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Gut Microbiota Disorder, Gut Epithelial and Blood–Brain Barrier Dysfunctions in Etiopathogenesis of Dementia: Molecular Mechanisms and Signaling Pathways

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Abstract

Emerging evidences indicate a critical role of the gut microbiota in etiopathogenesis of dementia, a debilitating multifactorial disorder characterized by progressive deterioration of cognition and behavior that interferes with the social and professional functions of the sufferer. Available data suggest that gut microbiota disorder that triggers development of dementia is characterized by substantial reduction in specific species belonging to the Firmicutes and Bacteroidetes phyla and presence of pathogenic species, predominantly, pro-inflammatory bacteria of the Proteobacteria phylum. These changes in gut microbiota microecology promote the production of toxic metabolites and pro-inflammatory cytokines, and reduction in beneficial substances such as short chain fatty acids and other anti-inflammatory factors, thereby, enhancing destruction of the gut epithelial barrier with concomitant activation of local and distant immune cells as well as dysregulation of enteric neurons and glia. This subsequently leads to blood–brain barrier dysfunctions that trigger neuroinflammatory reactions and predisposes to apoptotic neuronal and glial cell death, particularly in the hippocampus and cerebral cortex, which underlie the development of dementia. However, the molecular switches that control these processes in the histo-hematic barriers of the gut and brain are not exactly known. This review integrates very recent data on the molecular mechanisms that link gut microbiota disorder to gut epithelial and blood–brain barrier dysfunctions, underlying the development of dementia. The signaling pathways that link gut microbiota disorder with impairment in cognition and behavior are also discussed. The review also highlights potential therapeutic options for dementia.

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References

  • Akbari, E., Asemi, Z., Daneshvar Kakhaki, R., Bahmani, F., Kouchaki, E., Tamtaji, O. R., et al. (2016). Effect of probiotic supplementation on cognitive function and metabolic status in Alzheimer’s disease: A randomized, double-blind and controlled trial. Frontiers in Aging Neuroscience, 8, 256.

    Article  PubMed  PubMed Central  Google Scholar 

  • Akkasheh, G., Kashani-Poor, Z., Tajabadi-Ebrahimi, M., Jafari, P., Akbari, H., Taghizadeh, M., et al. (2016). Clinical and metabolic response to probiotic administration in patients with major depressive disorder: A randomized, double-blind, placebo-controlled trial. Nutrition, 32(3), 315–320. https://doi.org/10.1016/j.nut.2015.09.003.

    Article  CAS  PubMed  Google Scholar 

  • Alhasson, F., Das, S., Seth, R., Dattaroy, D., Chandrashekaran, V., Ryan, C. N., et al. (2017). Altered gut microbiome in a mouse model of Gulf War Illness causes neuroinflammation and intestinal injury via leaky gut and TLR4 activation. PLoS ONE, 12(3), e0172914.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alkasir, R., Li, J., Li, X., Jin, M., & Zhu, B. (2017). Human gut microbiota: The links with dementia development. Protein Cell, 8(2), 90–102.

    Article  CAS  PubMed  Google Scholar 

  • Almeida, O. P., & Lautenschlager, N. T. (2005). Dementia associated with infectious diseases. International Psychogeriatrics, 17(Suppl 1), S65–S77.

    Article  PubMed  Google Scholar 

  • Amasheh, S., Fromm, M., & Günzel, D. (2011). Claudins of intestine and nephron: A correlation of molecular tight junction structure and barrier function. Acta Psychologica, 201(1), 133–140.

    CAS  Google Scholar 

  • Araos, R., Andreatos, N., Ugalde, J., Mitchell, S., Mylonakis, E., & D’Agata, E. M. C. (2018). Fecal microbiome among nursing home residents with advanced dementia and Clostridium difficile. Digestive Diseases and Sciences., 63, 1525–1531. https://doi.org/10.1007/s10620-018-5030-7.

    Article  PubMed  PubMed Central  Google Scholar 

  • Asgari, E., Farrar, C. A., Lynch, N., Ali, Y. M., Roscher, S., Stover, C., et al. (2014). Mannan-binding lectin-associated serine protease 2 is critical for the development of renal ischemia reperfusion injury and mediates tissue injury in the absence of complement C4. The THE FASEB JOURNALournal, 28(9), 3996–4003.

    Article  CAS  Google Scholar 

  • Awad, W. A., Hess, C., & Hess, M. (2017). Enteric pathogens and their toxin-induced disruption of the intestinal barrier through alteration of tight junctions in chickens. Toxins (Basel), 9(2), 60.

    Article  Google Scholar 

  • Bambury, A., Sandhu, K., Cryan, J. F., & Dinan, T. G. (2018). Finding the needle in the haystack: Systematic identification of psychobiotics. British Journal of Pharmacology., 175, 4430–4438. https://doi.org/10.1111/bph.14127.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bäuerl, C., Collado, M. C., Diaz Cuevas, A., Viña, J., & Pérez Martínez, G. (2018). Shifts in gut microbiota composition in an APP/PSS1 transgenic mouse model of Alzheimer’s disease during lifespan. Letters in Applied Microbiology., 66, 464–471. https://doi.org/10.1111/lam.12882.

    Article  CAS  PubMed  Google Scholar 

  • Bayliss, J. A., Lemus, M., Santos, V. V., Deo, M., Elsworth, J. D., & Andrews, Z. B. (2016). Acylated but not des-acyl ghrelin is neuroprotective in an MPTP mouse model of Parkinson’s disease. Journal of Neurochemistry, 137, 460–471.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bhat, M. I., & Kapila, R. (2017). Dietary metabolites derived from gut microbiota: Critical modulators of epigenetic changes in mammals. Nutrition Reviews, 75(5), 374–389.

    Article  PubMed  Google Scholar 

  • Bjarnadottir, H., Arnardottir, M., & Ludviksson, B. R. (2016). Frequency and distribution of FCN2 and FCN3 functional variants among MBL2 genotypes. Immunogenetics, 68, 315–325.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bonder, M. J., Kurilshikov, A., Tigchelaar, E. F., Mujagic, Z., Imhann, F., Vila, A. V., et al. (2016). The effect of host genetics on the gut microbiome. Nature Genetics, 48(11), 1407–1412.

    Article  CAS  PubMed  Google Scholar 

  • Bonfili, L., Cecarini, V., Berardi, S., Scarpona, S., Suchodolski, J. S., Nasuti, C., et al. (2017). Microbiota modulation counteracts Alzheimer’s disease progression influencing neuronal proteolysis and gut hormones plasma levels. Scientific Report, 7, 2426.

    Article  CAS  Google Scholar 

  • Bonfili, L., Cecarini, V., Cuccioloni, M., Angeletti, M., Berardi, S., Scarpona, S., et al. (2018). SLAB51 probiotic formulation activates SIRT1 pathway promoting antioxidant and neuroprotective effects in an AD mouse model. Molecular Neurobiology, 55(10), 7987–8000.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brady, A. M., Geno, K. A., Dalecki, A. G., Cheng, X., & Nahm, M. H. (2014). Commercially available complement component-depleted sera are unexpectedly codepleted of ficolin-2. Clinical and Vaccine Immunology, 21(9), 1323–1329.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Braniste, V., Al-Asmakh, M., Kowal, C., Anuar, F., Abbaspour, A., Tóth, M., et al. (2014). The gut microbiota influences blood–brain barrier permeability in mice. Science Translational Medicine, 6(263), 263ra158.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Britton, E., & McLaughlin, J. T. (2013). Ageing and the gut. Proceedings of the Nutrition Society, 72(1), 173–177.

    Article  PubMed  Google Scholar 

  • Browne, T. C., McQuillan, K., McManus, R. M., O’Reilly, J. A., Mills, K. H., & Lynch, M. A. (2013). IFN-γ Production by amyloid β-specific Th1 cells promotes microglial activation and increases plaque burden in a mouse model of Alzheimer’s disease. Journal of Immunology, 190(5), 2241–2251.

    Article  CAS  Google Scholar 

  • Buford, T. W. (2017). (Dis)Trust your gut: The gut microbiome in age-related inflammation, health, and disease. Microbiome, 5, 80.

    Article  PubMed  PubMed Central  Google Scholar 

  • Burokas, A., Arboleya, S., Moloney, R. D., Peterson, V. L., Murphy, K., Clarke, G., et al. (2017). Targeting the microbiota–gut–brain axis: Prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice. Biological Psychiatry, 82(7), 472–487.

    Article  CAS  PubMed  Google Scholar 

  • Butterfield, D. A., & Boyd-Kimball, D. (2018). Oxidative stress, amyloid-β peptide, and altered key molecular pathways in the pathogenesis and progression of Alzheimer’s disease. Journal of Alzheimer’s Disease, 62(3), 1345–1367.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cai, Z., Hussain, M. D., & Yan, L. J. (2014a). Microglia, neuroinflammation, and beta-amyloid protein in Alzheimer’s disease. International Journal of Neuroscience, 124(5), 307–321.

    Article  CAS  PubMed  Google Scholar 

  • Cai, W., Uribarri, J., Zhu, L., Chen, X., Swamy, S., Zhao, Z., et al. (2014b). Oral glycotoxins are a modifiable cause of dementia and the metabolic syndrome in mice and humans. Proceedings of the National Academy of Sciences of the United States of America, 111(13), 4940–4945.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Canani, R. B., Costanzo, M. D., Leone, L., Bedogni, G., Brambilla, P., Cianfarani, S., et al. (2011). Epigenetic mechanisms elicited by nutrition in early life. Nutrition Research Reviews, 24(2), 198–205.

    Article  CAS  PubMed  Google Scholar 

  • Capaldo, C. T., Powell, D. N., & Kalman, D. (2017). Layered defense: How mucus and tight junctions seal the intestinal barrier. Journal of Molecular Medicine (Berlin), 95(9), 927–934.

    Article  CAS  Google Scholar 

  • Cattaneo, A., Cattane, N., Galluzzi, S., Provasi, S., Lopizzo, N., Festari, C., et al. (2017). INDIA-FBP Group. Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly. Neurobiology of Aging, 49, 60–68.

    Article  CAS  PubMed  Google Scholar 

  • Ceccarelli, G., Brenchley, J. M., Cavallari, E. N., Scheri, G. C., Fratino, M., Pinacchio, C., et al. (2017). Impact of high-dose multi-strain probiotic supplementation on neurocognitive performance and central nervous system immune activation of HIV-1 infected individuals. Nutrients, 9(11), 1269.

    Article  CAS  PubMed Central  Google Scholar 

  • Cenit, M. C., Sanz, Y., & Codoñer-Franch, P. (2017). Influence of gut microbiota on neuropsychiatric disorders. World Journal of Gastroenterology, 23(30), 5486–5498.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chaudhuri, K., Samarakoon, S. M. S., Chandola, H. M., Kumar, R., & Ravishankar, B. (2011). Evaluation of diet and life style in etiopathogenesis of senile dementia: A survey study. Ayu, 32(2), 171–176.

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen, W. W., Zhang, X., & Huang, W. J. (2016). Role of neuroinflammation in neurodegenerative diseases (Review). Molecular Medicine Reports, 13(4), 3391–3396.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheng, D., Wang, X., Xi, Y., Cao, J., & Jiang, W. (2017). Identification of the Al-binding proteins that account for aluminum neurotoxicity and transport in vivo. Toxicol Research (Cambridge), 7(1), 127–135.

    Article  Google Scholar 

  • Chertkow, H., Feldman, H. H., Jacova, C., & Massoud, F. (2013). Definitions of dementia and predementia states in Alzheimer’s disease and vascular cognitive impairment: Consensus from the Canadian conference on diagnosis of dementia. Alzheimer’s Research & Therapy, 5(Suppl 1), S2.

    Article  Google Scholar 

  • Chia, W. J., Tan, F. C., Ong, W. Y., & Dawe, G. S. (2015). Expression and localisation of brain-type organic cation transporter (BOCT/24p3R/LCN2R) in the normal rat hippocampus and after kainate-induced excitotoxicity. Neurochemistry International, 87, 43–59.

    Article  CAS  PubMed  Google Scholar 

  • Chiappelli, F. (2018). Advances in psychobiology. New York: Nova Science Publishers.

    Google Scholar 

  • Chin-Chan, M., Navarro-Yepes, J., & Quintanilla-Vega, B. (2015). Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases. Frontiers in Cellular Neuroscience, 9, 124.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chio, C. C., Chang, C. H., Wang, C. C., Cheong, C. U., Chao, C. M., Cheng, B. C., et al. (2013). Etanercept attenuates traumatic brain injury in rats by reducing early microglial expression of tumor necrosis factor-α. BMC Neuroscience, 14, 33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chunchai, T., Thunapong, W., Yasom, S., Wanchai, K., Eaimworawuthikul, S., Metzler, G., et al. (2018). Decreased microglial activation through gut–brain axis by prebiotics, probiotics, or synbiotics effectively restored cognitive function in obese-insulin resistant rats. Journal of Neuroinflammation, 15, 11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clark, A., & Mach, N. (2016). Exercise-induced stress behavior, gut-microbiota-brain axis and diet: A systematic review for athletes. Journal of the International Society of Sports Nutrition, 13, 43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clarke, G., Stilling, R. M., Kennedy, P. J., Stanton, C., Cryan, J. F., & Dinan, T. G. (2014). Gut microbiota: The neglected endocrine organ. Molecular Endocrinology, 28(8), 1221–1238.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cong, X., Judge, M., Xu, W., Diallo, A., Janton, S., Brownell, E. A., et al. (2017). Influence of feeding type on gut microbiome development in hospitalized preterm infants. Nursing Research, 66(2), 123–133.

    Article  PubMed  PubMed Central  Google Scholar 

  • Coppo, R. (2018). The gut-kidney axis in IgA nephropathy: Role of microbiota and diet on genetic predisposition. Pediatric Nephrology (Berlin, Germany), 33(1), 53–61.

    Article  Google Scholar 

  • Coraci, I. S., Husemann, J., Berman, J. W., Hulette, C., Dufour, J. H., Campanella, G. K., et al. (2002). CD36, a class B scavenger receptor, is expressed on microglia in Alzheimer’s disease brains and can mediate production of reactive oxygen species in response to beta-amyloid fibrils. American Journal of Pathology, 160(1), 101–112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Corraini, P., Henderson, V. W., Ording, A. G., Pedersen, L., Horváth-Puhó, E., & Sørensen, H. T. (2017). Long-term risk of dementia among survivors of ischemic or hemorrhagic stroke. Stroke, 48(1), 180–186.

    Article  CAS  PubMed  Google Scholar 

  • Crehan, H., Hardy, J., & Pocock, J. (2012). Microglia, Alzheimer’s disease, and complement. International Journal of Alzheimer’s Disease, 2012, 983640.

    PubMed  PubMed Central  Google Scholar 

  • Cristiano, C., Lama, A., Lembo, F., Mollica, M. P., Calignano, A., & Mattace Raso, G. (2018). Interplay between peripheral and central inflammation in autism spectrum disorders: Possible nutritional and therapeutic strategies. Frontiers Physiology, 9, 184.

    Article  Google Scholar 

  • Cupidi, C., Frangipane, F., Gallo, M., Clodomiro, A., Colao, R., Bernardi, L., et al. (2017). Role of Niemann-Pick Type C disease mutations in dementia. Journal of Alzheimer’s Disease, 55(3), 1249–1259.

    Article  CAS  PubMed  Google Scholar 

  • Daulatzai, M. A. (2014). Obesity and gut’s dysbiosis promote neuroinflammation, cognitive impairment, and vulnerability to Alzheimer’s disease: New directions and therapeutic implications. Journal of Molecular and Genetic Medicine, 1, 005. https://doi.org/10.4172/1747-0862.S1-005.

    Article  Google Scholar 

  • Davenport, E. R., Cusanovich, D. A., Michelini, K., Barreiro, L. B., Ober, C., & Gilad, Y. (2015). Genome-wide association studies of the human gut microbiota. PLoS ONE, 10(11), e0140301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • David, L. A., Maurice, C. F., Carmody, R. N., Gootenberg, D. B., Button, J. E., Wolfe, B. E., et al. (2014). Diet rapidly and reproducibly alters the human gut microbiome. Nature, 505(7484), 559–563.

    Article  CAS  PubMed  Google Scholar 

  • de Jager, C. A., Msemburi, W., Pepper, K., & Combrinck, M. I. (2017). Dementia prevalence in a rural region of South Africa: A cross-sectional community study. Journal of Alzheimer’s Disease, 60(3), 1087–1096.

    Article  PubMed  PubMed Central  Google Scholar 

  • De Preter, V., Vanhoutte, T., Huys, G., Swings, J., Rutgeerts, P., & Verbeke, K. (2006). Effect of lactulose and Saccharomyces boulardii administration on the colonic urea-nitrogen metabolism and the bifidobacteria concentration in healthy human subjects. Alimentary Pharmacology & Therapeutics, 23(7), 963–974.

    Article  CAS  Google Scholar 

  • Degn, S. E., Jensen, L., Olszowski, T., Jensenius, J. C., & Thiel, S. (2013). Co-complexes of MASP-1 and MASP-2 associated with the soluble pattern-recognition molecules drive lectin pathway activation in a manner inhibitable by MAp44. Journal of Immunology, 191(3), 1334–1345.

    Article  CAS  Google Scholar 

  • Di Fede, G., Giaccone, G., Salmona, M., & Tagliavini, F. (2018). Translational research in Alzheimer’s and Prion diseases. Journal of Alzheimer’s Disease, 62(3), 1247–1259.

    Article  PubMed  PubMed Central  Google Scholar 

  • Di Lorenzo, F., & Di Lorenzo, B. (2013). Iron and aluminum in Alzheimer’s disease. Neuroendocrinology Letters, 34(6), 504–507.

    PubMed  Google Scholar 

  • Dinan, T. G., & Cryan, J. F. (2017). Gut instincts: Microbiota as a key regulator of brain development, ageing and neurodegeneration. Journal of Physiology, 595(2), 489–503.

    Article  CAS  PubMed  Google Scholar 

  • Doens, D., & Fernández, P. L. (2014). Microglia receptors and their implications in the response to amyloid β for Alzheimer’s disease pathogenesis. Journal of Neuroinflammation, 11, 48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dong, S., Duan, Y., Hu, Y., & Zhao, Z. (2012). Advances in the pathogenesis of Alzheimer’s disease: A re-evaluation of amyloid cascade hypothesis. Translational Neurodegeneration, 1, 18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dong, J., Robertson, J. D., Markesbery, W. R., & Lovell, M. A. (2008). Serum zinc in the progression of Alzheimer’s disease. Journal of Alzheimer’s Disease, 15(3), 443–450.

    Article  CAS  PubMed  Google Scholar 

  • Du, X., Wang, X., & Geng, M. (2018). Alzheimer’s disease hypothesis and related therapies. Translational Neurodegeneration, 7, 2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dunn, N., Mullee, M., Perry, V. H., & Holmes, C. (2005). Association between dementia and infectious disease: Evidence from a case-control study. Alzheimer Disease and Associated Disorders, 19(2), 91–94.

    Article  PubMed  Google Scholar 

  • El Khoury, J., Hickman, S. E., Thomas, C. A., Loike, J. D., & Silverstein, S. C. (1998). Microglia, scavenger receptors, and the pathogenesis of Alzheimer’s disease. Neurobiology of Aging, 19(1 Suppl), S81–S84.

    Article  PubMed  Google Scholar 

  • Engel, G. L. (1954). Studies of ulcerative colitis. II. The nature of the somatic processes and the adequacy of psychosomatic hypotheses. American Journal of Medicine, 16, 416–433.

    Article  CAS  PubMed  Google Scholar 

  • Erdő, F., Denes, L., & de Lange, E. (2017). Age-associated physiological and pathological changes at the blood–brain barrier: A review. Journal of Cerebral Blood Flow and Metabolism, 37(1), 4–24.

    Article  PubMed  Google Scholar 

  • Evans, P. H. (1993). Free radicals in brain metabolism and pathology. British Medical Bulletin, 49(3), 577–587.

    Article  CAS  PubMed  Google Scholar 

  • Evans, P. H., Klinowski, J., & Yano, E. (1991). Cephaloconiosis: A free radical perspective on the proposed particulate-induced etiopathogenesis of Alzheimer’s dementia and related disorders. Medical Hypotheses, 34(3), 209–219.

    Article  CAS  PubMed  Google Scholar 

  • Evans, P. H., Yano, E., Klinowski, J., & Peterhans, E. (1992). Oxidative damage in Alzheimer’s dementia, and the potential etiopathogenic role of aluminosilicates, microglia and micronutrient interactions. EXS, 62, 178–189.

    CAS  PubMed  Google Scholar 

  • Fang, X. (2016). Potential role of gut microbiota and tissue barriers in Parkinson’s disease and amyotrophic lateral sclerosis. International Journal of Neuroscience, 126(9), 771–776.

    Article  CAS  PubMed  Google Scholar 

  • Farzi, A., Fröhlich, E. E., & Holzer, P. (2018). Gut microbiota and the neuroendocrine system. Neurotherapeutics, 15(1), 5–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fattahi, M. J., & Mirshafiey, A. (2014). Positive and negative effects of prostaglandins in Alzheimer’s disease. Psychiatry and Clinical Neurosciences, 68(1), 50–60.

    Article  CAS  PubMed  Google Scholar 

  • Fernandez-Prado, R., Esteras, R., Perez-Gomez, M. V., Gracia-Iguacel, C., Gonzalez-Parra, E., Sanz, A. B., et al. (2017). Nutrients turned into toxins: Microbiota modulation of nutrient properties in chronic kidney disease. Nutrients, 9(5), 489.

    Article  CAS  PubMed Central  Google Scholar 

  • Fiebich, B. L., Schleicher, S., Spleiss, O., Czygan, M., & Hüll, M. (2001). Mechanisms of prostaglandin E2-induced interleukin-6 release in astrocytes: Possible involvement of EP4-like receptors, p38 mitogen-activated protein kinase and protein kinase C. Journal of Neurochemistry, 79(5), 950–958.

    Article  CAS  PubMed  Google Scholar 

  • Fiest, K. M., Jetté, N., Roberts, J. I., Maxwell, C. J., Smith, E. E., Black, S. E., et al. (2016). The prevalence and incidence of dementia: A systematic review and meta-analysis. Canadian Journal of Neurological Sciences, 43(1), S3–S50.

    Article  Google Scholar 

  • Figarska, S. M., Vonk, J. M., & Boezen, H. M. (2014). NFE2L2 polymorphisms, mortality, and metabolism in the general population. Physiological Genomics, 46(12), 411–417.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Förster, C. (2008). Tight junctions and the modulation of barrier function in disease. Histochemistry and Cell Biology, 130(1), 55–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Foster, J. A., Rinaman, L., & Cryan, J. F. (2017). Stress & the gut–brain axis: Regulation by the microbiome. Neurobiology of Stress, 7, 124–136.

    Article  PubMed  PubMed Central  Google Scholar 

  • Fransen, F., van Beek, A. A., Borghuis, T., El Aidy, S., Hugenholtz, F., van der Gaast, et al. (2017). Aged gut microbiota contributes to systemical inflammaging after transfer to germ-free mice. Frontiers in Immunology, 8, 1385.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fratiglioni, L., De Ronchi, D., & Agüero-Torres, H. (1999). Worldwide prevalence and incidence of dementia. Drugs and Aging, 15(5), 365–375.

    Article  CAS  PubMed  Google Scholar 

  • Friedland, R. P., & Chapman, M. R. (2017). The role of microbial amyloid in neurodegeneration. PLoS Pathogens, 13(12), e1006654.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gambuzza, M. E., Sofo, V., Salmeri, F. M., Soraci, L., Marino, S., & Bramanti, P. (2014). Toll-like receptors in Alzheimer’s disease: A therapeutic perspective. CNS & Neurological Disorders: Drug Targets, 13(9), 1542–1558.

    Article  CAS  Google Scholar 

  • Genuis, S. J., & Kelln, K. L. (2015). Toxicant exposure and bioaccumulation: A common and potentially reversible cause of cognitive dysfunction and dementia. Behavioural Neurology, 2015, 620143.

    Article  PubMed  PubMed Central  Google Scholar 

  • Geschwind, M. D. (2010). Rapidly progressive dementia: Prion diseases and other rapid dementias. Continuum (Minneap Minn)., 16(2), 31–56.

    PubMed  Google Scholar 

  • Ghaisas, S., Maher, J., & Kanthasamy, A. (2016). Gut microbiome in health and disease: Linking the microbiome–gut–brain axis and environmental factors in the pathogenesis of systemic and neurodegenerative diseases. Pharmacology & Therapeutics, 158, 52–62.

    Article  CAS  Google Scholar 

  • Ghosh, S., Wu, M. D., Shaftel, S. S., Kyrkanides, S., LaFerla, F. M., Olschowka, J. A., et al. (2013). Sustained interleukin-1β overexpression exacerbates tau pathology despite reduced amyloid burden in an Alzheimer’s mouse model. Journal of Neuroscience, 33(11), 5053–5064.

    Article  CAS  PubMed  Google Scholar 

  • Gordon, S. (2002). Pattern recognition receptors: Doubling up for the innate immune response. Cell, 111(7), 927–930.

    Article  CAS  PubMed  Google Scholar 

  • Griñán-Ferré, C., Corpas, R., Puigoriol-Illamola, D., Palomera-Ávalos, V., Sanfeliu, C., & Pallàs, M. (2018). Understanding epigenetics in the neurodegeneration of Alzheimer’s disease: SAMP8 mouse model. Journal of Alzheimer’s Disease, 62(3), 943–963.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hanamsagar, R., Hanke, M. L., & Kielian, T. (2012). Toll-like receptor (TLR) and inflammasome actions in the central nervous system. Trends in Immunology, 33(7), 333–342.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hang, L., Basil, A. H., & Lim, K.-L. (2016). Nutraceuticals in Parkinson’s disease. Neuromolecular Medicine, 18, 306–321.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hartz, A., Pagel, J., Humberg, A., Preuss, M., Schreiter, L., Rupp, J., et al. (2017). The association of mannose-binding lectin 2 polymorphisms with outcome in very low birth weight infants. PLoS ONE, 12(5), e0178032.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hasan, M. K., Liu, C., Wang, F., Ahammed, G. J., Zhou, J., Xu, M. X., et al. (2016). Glutathione-mediated regulation of nitric oxide, S-nitrosothiol and redox homeostasis confers cadmium tolerance by inducing transcription factors and stress response genes in tomato. Chemosphere, 161, 536–545.

    Article  CAS  PubMed  Google Scholar 

  • Héja, D., Kocsis, A., Dobó, J., Szilágyi, K., Szász, R., Závodszky, P., et al. (2012). Revised mechanism of complement lectin-pathway activation revealing the role of serine protease MASP-1 as the exclusive activator of MASP-2. Proceedings of the National Academy of Sciences of the United States of America, 109(26), 10498–10503.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hickman, S. E., Allison, E. K., & El Khoury, J. (2008). Microglial dysfunction and defective β-amyloid clearance pathways in aging Alzheimer’s disease mice. Journal of Neuroscience, 28(33), 8354–8360.

    Article  CAS  PubMed  Google Scholar 

  • Ho, J. T. K., Chan, G. C. F., & Li, J. C. B. (2015). Systemic effects of gut microbiota and its relationship with disease and modulation. BMC Immunology, 16, 21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Houghteling, P. D., & Walker, W. A. (2015). Why is initial bacterial colonization of the intestine important to the infant’s and child’s health? Journal of Pediatric Gastroenterology and Nutrition, 60(3), 294–307.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hoyles, L., Snelling, T., Umlai, U. K., Nicholson, J. K., Carding, S. R., Glen, R. C., et al. (2018). Microbiome-host systems interactions: Protective effects of propionate upon the blood–brain barrier. Microbiome, 6(1), 55.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hu, N., Tan, M.-S., Sun, L., Jiang, T., Wang, Y.-L., Tan, L., et al. (2014). Decreased expression of CD33 in peripheral mononuclear cells of Alzheimer’s disease patients. Neuroscience Letters, 563, 51–54.

    Article  CAS  PubMed  Google Scholar 

  • Hu, X., Wang, T., & Jin, F. (2016). Alzheimer’s disease and gut microbiota. Science China Life Sciences, 59(10), 1006–1023.

    Article  CAS  PubMed  Google Scholar 

  • Hulse, G. K., Lautenschlager, N. T., Tait, R. J., & Almeida, O. P. (2005). Dementia associated with alcohol and other drug use. International Psychogeriatrics, 17(1), S109–S127.

    Article  PubMed  Google Scholar 

  • Hung, Y.-N., Kadziola, Z., Brnabic, A. J. M., Yeh, J.-F., Fuh, J.-L., Hwang, J.-P., et al. (2016). The epidemiology and burden of Alzheimer’s disease in Taiwan utilizing data from the National Health Insurance Research Database. ClinicoEconomics and Outcomes Research, 8, 387–395.

    Article  PubMed  PubMed Central  Google Scholar 

  • Huo, R., Zeng, B., Zeng, L., Cheng, K., Li, B., Luo, Y., et al. (2017). Microbiota modulate anxiety-like behavior and endocrine abnormalities in hypothalamic-pituitary-adrenal axis. Frontiers in Cellular and Infection Microbiology, 7, 489. https://doi.org/10.3389/fcimb.2017.00489.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hwang, S., Lim, J. W., & Kim, H. (2017). Inhibitory effect of lycopene on amyloid-β-induced apoptosis in neuronal cells. Nutrients, 9(8), 883.

    Article  CAS  PubMed Central  Google Scholar 

  • Iemolo, F., Duro, G., Rizzo, C., Castiglia, L., Hachinski, V., & Caruso, C. (2009). Pathophysiology of vascular dementia. Immunity & Ageing, 6, 13.

    Article  CAS  Google Scholar 

  • Inglese, M., & Petracca, M. (2013). Imaging multiple sclerosis and other neurodegenerative diseases. Prion, 7(1), 47–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jacobson, A., Lam, L., Rajendram, M., Tamburini, F., Honeycutt, J., Pham, T., et al. (2018). A gut commensal-produced metabolite mediates colonization resistance to salmonella infection. Cell Host & Microbe, 24(2), 296–307.

    Article  CAS  Google Scholar 

  • James, B. D., & Schneider, J. A. (2010). Increasing incidence of dementia in the oldest old: Evidence and implications. Alzheimer’s Research & Therapy, 2, 9.

    Article  Google Scholar 

  • Jamilian, M., Bahmani, F., Vahedpoor, Z., Salmani, A., Tajabadi-Ebrahimi, M., Jafari, P., et al. (2016). Effects of probiotic supplementation on metabolic status in pregnant women: A randomized, double-blind, placebo-controlled trial. Archives of Iranian Medicine, 19(10), 687–692.

    PubMed  Google Scholar 

  • Jana, M., Palencia, C. A., & Pahan, K. (2008). Fibrillar amyloid-β peptides activate microglia via TLR2: Implications for Alzheimer’s disease. Journal of Immunology, 181(10), 7254–7262.

    Article  CAS  Google Scholar 

  • Jiang, C., Li, G., Huang, P., Liu, Z., & Zhao, B. (2017). The gut microbiota and Alzheimer’s disease. Journal of Alzheimer’s Disease, 58(1), 1–15.

    Article  CAS  PubMed  Google Scholar 

  • Jo, E.-K., Kim, J. K., Shin, D.-M., & Sasakawa, C. (2016). Molecular mechanisms regulating NLRP3 inflammasome activation. Cellular & Molecular Immunology, 13(2), 148–159.

    Article  CAS  Google Scholar 

  • Johnell, K. (2015). Inappropriate drug use in people with cognitive impairment and dementia: A systematic review. Current Clinical Pharmacology, 10(3), 178–184.

    Article  PubMed  PubMed Central  Google Scholar 

  • Juárez-Rebollar, D., Rios, C., Nava-Ruíz, C., & Méndez-Armenta, M. (2017). Metallothionein in brain disorders. Oxidative Medicine and Cellular Longevity, 2017, 5828056.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kalantari, P. (2018). The emerging role of pattern recognition receptors in the pathogenesis of malaria. Vaccines, 6(1), 13. https://doi.org/10.3390/vaccines6010013.

    Article  CAS  PubMed Central  Google Scholar 

  • Kalaria, R. N. (2016). Neuropathological diagnosis of vascular cognitive impairment and vascular dementia with implications for Alzheimer’s disease. Acta Neuropathologica, 131, 659–685.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kang, D.-W., Adams, J. B., Gregory, A. C., Borody, T., Chittick, L., Fasano, A., et al. (2017). Microbiota transfer therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: An open-label study. Microbiome, 5, 10.

    Article  PubMed  PubMed Central  Google Scholar 

  • Katan, M., Moon, Y. P., Paik, M. C., Sacco, R. L., Wright, C. B., & Elkind, M. S. V. (2013). Infectious burden and cognitive function: The Northern Manhattan study. Neurology, 80(13), 1209–1215.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kaushal, V., Dye, R., Pakavathkumar, P., Foveau, B., Flores, J., Hyman, B., et al. (2015). Neuronal NLRP1 inflammasome activation of Caspase-1 coordinately regulates inflammatory interleukin-1-beta production and axonal degeneration-associated Caspase-6 activation. Cell Death and Differentiation, 22(10), 1676–1686.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kelly, J. R., Kennedy, P. J., Cryan, J. F., Dinan, T. G., Clarke, G., & Hyland, N. P. (2015). Breaking down the barriers: The gut microbiome, intestinal permeability and stress-related psychiatric disorders. Frontiers in Cellular Neuroscience, 9, 392.

    PubMed  PubMed Central  Google Scholar 

  • Killin, L. O. J., Starr, J. M., Shiue, I. J., & Russ, T. C. (2016). Environmental risk factors for dementia: A systematic review. BMC Geriatrics, 16, 175.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kilpatrick, D. C., & Chalmers, J. D. (2012). Human L-ficolin (ficolin-2) and its clinical significance. Journal of Biomedicine and Biotechnology, 2012, 138797.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim, S.-H., Turnbull, J., & Guimond, S. (2011). Extracellular matrix and cell signalling: The dynamic cooperation of integrin, proteoglycan and growth factor receptor. Journal of Endocrinology, 209, 139–151.

    Article  CAS  PubMed  Google Scholar 

  • Kjeldsen, L., Johnsen, A. H., Sengeløv, H., & Borregaard, N. (1993). Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase. Journal of Biological Chemistry, 268(14), 10425–10432.

    CAS  PubMed  Google Scholar 

  • Knopman, D. S. (2006). Dementia and cerebrovascular disease. Mayo Clinic Proceedings, 81(2), 223–230.

    Article  PubMed  Google Scholar 

  • Kobylecki, C., Jones, M., Thompson, J. C., Richardson, A. M., Neary, D., Mann, D. M. A., et al. (2015). Cognitive-behavioural features of progressive supranuclear palsy syndrome overlap with frontotemporal dementia. Journal of Neurology, 262(4), 916–922.

    Article  PubMed  Google Scholar 

  • Koedrith, P., & Seo, Y. R. (2011). Advances in carcinogenic metal toxicity and potential molecular markers. International Journal of Molecular Sciences, 12(12), 9576–9595.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kumar, H., Lund, R., Laiho, A., Lundelin, K., Ley, R. E., Isolauri, E., et al. (2014). Gut microbiota as an epigenetic regulator: Pilot study based on whole-genome methylation analysis. MBio, 5(6), e02113–e02114. https://doi.org/10.1128/mbio.02113-14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lach, G., Schellekens, H., Dinan, T. G., & Cryan, J. F. (2018). Anxiety, depression, and the microbiome: A role for gut peptides. Neurotherapeutics, 15(1), 36–59.

    Article  CAS  PubMed  Google Scholar 

  • Land, W. G. (2015). The role of damage-associated molecular patterns (DAMPs) in human diseases Part II: DAMPs as diagnostics, prognostics and therapeutics in clinical medicine. Sultan Qaboos University Medical Journal, 15(2), e157–e170.

    PubMed  PubMed Central  Google Scholar 

  • Lee, S., Kim, J. H., Kim, J. H., Seo, J. W., Han, H. S., Lee, W. H., et al. (2011). Lipocalin-2 Is a chemokine inducer in the central nervous system: Role of chemokine ligand 10 (CXCL10) in lipocalin-2-induced cell migration. Journal of Biological Chemistry, 286(51), 43855–43870.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee, S., Lee, W. H., Lee, M. S., Mori, K., & Suk, K. (2012). Regulation by lipocalin-2 of neuronal cell death, migration, and morphology. Journal of Neuroscience Research, 90(3), 540–550.

    Article  CAS  PubMed  Google Scholar 

  • Lee, E. S., Song, E. J., & Nam, Y. D. (2017). Dysbiosis of gut microbiome and its impact on epigenetic regulation. Journal of Clinical Epigenetics, 3, S1.

    Google Scholar 

  • Leverenz, J. B., Quinn, J. F., Zabetian, C., Zhang, J., Montine, K. S., & Montine, T. J. (2009). Cognitive impairment and dementia in patients with Parkinson disease. Current Topics in Medicinal Chemistry, 9(10), 903–912.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lewis, K. N., Mele, J., Hayes, J. D., & Buffenstein, R. (2010). Nrf2, a guardian of healthspan and gatekeeper of species longevity. Integrative and Comparative Biology, 50(5), 829–843.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li, M.-F., Li, Jun, & Sun, Li. (2016). CsMAP34, a teleost MAP with dual role: A promoter of MASP-assisted complement activation and a regulator of immune cell activity. Scientific Report, 6, 39287.

    Article  CAS  Google Scholar 

  • Li, X., Melief, E., Postupna, N., Montine, K. S., Keene, C. D., & Montine, T. J. (2015). Prostaglandin E2 receptor subtype 2 regulation of scavenger receptor CD36 modulates microglial Aβ42 phagocytosis. American Journal of Pathology, 185(1), 230–239.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li, D.-D., Zhang, W., Wang, Z.-Y., & Zhao, P. (2017). Serum copper, zinc, and iron levels in patients with Alzheimer’s disease: A meta-analysis of case-control studies. Frontiers in Aging Neuroscience, 9, 300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lian, H., Litvinchuk, A., Chiang, A. C., Aithmitti, N., Jankowsky, J. L., & Zheng, H. (2016). Astrocyte-microglia cross talk through complement activation modulates amyloid pathology in mouse models of Alzheimer’s disease. Journal of Neuroscience, 36(2), 577–589.

    Article  CAS  PubMed  Google Scholar 

  • Liang, X., Wang, Q., Hand, T., Wu, L., Breyer, R. M., Montine, T. J., et al. (2005). Deletion of the prostaglandin E2 EP2 receptor reduces oxidative damage and amyloid burden in a model of Alzheimer’s disease. Journal of Neuroscience, 25(44), 10180–10187.

    Article  CAS  PubMed  Google Scholar 

  • Licastro, F., & Porcellini, E. (2016). Persistent infections, immune-senescence and Alzheimer’s disease. Oncoscience, 3(5–6), 135–142.

    PubMed  PubMed Central  Google Scholar 

  • Lin, H. V., Frassetto, A., Kowalik, E. J., Jr., Nawrocki, A. R., Lu, M. M., Kosinski, J. R., et al. (2012). Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS ONE, 7(4), e35240.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu, S., Liu, Y., Hao, W., Wolf, L., Kiliaan, A. J., Penke, B., et al. (2012). TLR2 is a primary receptor for Alzheimer’s amyloid β peptide to trigger neuroinflammatory activation. Journal of Immunology, 188(3), 1098–1107.

    Article  CAS  Google Scholar 

  • Luettig, J., Rosenthal, R., Barmeyer, C., & Schulzke, J. D. (2015). Claudin-2 as a mediator of leaky gut barrier during intestinal inflammation. Tissue Barriers, 3(1–2), e977176.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Magni, G., Bernasconi, G., Mauro, P., D’Odorico, A., Sturniolo, G. C., Canton, G., et al. (1991). Psychiatric diagnoses in ulcerative colitis. A controlled study. British Journal of Psychiatry, 158, 413–415.

    Article  CAS  Google Scholar 

  • Maguen, S., Madden, E., Cohen, B., Bertenthal, D., & Seal, K. (2014). Association of mental health problems with gastrointestinal disorders in Iraq and Afghanistan veterans. Depression and Anxiety, 31(2), 160–165.

    Article  PubMed  Google Scholar 

  • Mahla, R. S., Reddy, M. C., Prasad, D. V. R., & Kumar, H. (2013). Sweeten PAMPs: Role of sugar complexed PAMPs in innate immunity and vaccine biology. Frontiers in Immunology, 4, 248.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maloney, B., & Lahiri, D. K. (2016). Epigenetics of dementia: Understanding the disease as a transformation rather than a state. The Lancet Neurology, 15(7), 760–774.

    Article  CAS  PubMed  Google Scholar 

  • Mariadason, J. M., Barkla, D. H., & Gibson, P. R. (1997). Effect of short-chain fatty acids on paracellular permeability in Caco-2 intestinal epithelium model. American Journal of Physiology, 272, G705–G712.

    CAS  PubMed  Google Scholar 

  • Mariadason, J. M., Catto-Smith, A., & Gibson, P. R. (1999). Modulation of distal colonic epithelial barrier function by dietary fibre in normal rats. Gut, 44, 394–399.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martin, C. M. (2006). The “reversible” dementia of idiopathic normal pressure hydrocephalus. The Consultant pharmacist, 21(11), 888–893.

    Article  PubMed  Google Scholar 

  • Mattson, M. P., Barger, S. W., Cheng, B., Lieberburg, I., Smith-Swintosky, V. L., & Rydel, R. E. (1993). Beta-Amyloid precursor protein metabolites and loss of neuronal Ca2+ homeostasis in Alzheimer’s disease. Trends in Neurosciences, 16(10), 409–414.

    Article  CAS  PubMed  Google Scholar 

  • Mattsson, E., Heying, R., Van De Gevel, J. S., Hartung, T., & Beekhuizen, H. (2008). Staphylococcal peptidoglycan initiates an inflammatory response and procoagulant activity in human vascular endothelial cells: A comparison with highly purified lipoteichoic acid and TSST-1. FEMS Immunology and Medical Microbiology, 52(1), 110–117.

    Article  CAS  PubMed  Google Scholar 

  • Mawanda, F., & Wallace, R. (2013). Can infections cause Alzheimer’s disease? Epidemiologic Reviews, 35(1), 161–180.

    Article  PubMed  PubMed Central  Google Scholar 

  • McCarthy, C. G., Goulopoulou, S., Wenceslau, C. F., Spitler, K., Matsumoto, T., & Webb, R. C. (2014). Toll-like receptors and damage-associated molecular patterns: Novel links between inflammation and hypertension. American Journal of Physiology-Heart and Circulatory Physiology, 306(2), H184–H196.

    Article  CAS  PubMed  Google Scholar 

  • McKegney, F. P., Gordon, R. O., & Levine, S. M. (1970). A psychosomatic comparison of patients with ulcerative colitis and Crohn’s disease. Psychosomatic Medicine, 32, 153–166.

    Article  CAS  PubMed  Google Scholar 

  • Megyeri, M., Harmat, V., Major, B., Végh, Á., Balczer, J., Héja, D., et al. (2013). Quantitative characterization of the activation steps of mannan-binding lectin (MBL)-associated serine proteases (MASPs) points to the central role of MASP-1 in the initiation of the complement lectin pathway. Journal of Biological Chemistry, 288(13), 8922–8934.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Messaoudi, M., Lalonde, R., Violle, N., Javelot, H., Desor, D., Nejdi, A., et al. (2011). Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. British Journal of Nutrition, 105(5), 755–764.

    Article  CAS  PubMed  Google Scholar 

  • Millington, C., Sonego, S., Karunaweera, N., Rangel, A., Aldrich-Wright, J. R., Campbell, I. L., et al. (2014). Chronic neuroinflammation in Alzheimer’s disease: New perspectives on animal models and promising candidate drugs. BioMed Research International, 2014, 309129.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mishra, S., & Palanivelu, K. (2008). The effect of curcumin (turmeric) on Alzheimer’s disease: An overview. Annals of Indian Academy of Neurology, 11(1), 13–19.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mittermaier, C., Dejaco, C., Waldhoer, T., Oefferlbauer-Ernst, A., Miehsler, W., Beier, M., et al. (2004). Impact of depressive mood on relapse in patients with inflammatory bowel disease: A prospective 18-month follow-up study. Psychosomatic Medicine, 66(1), 79–84.

    Article  PubMed  Google Scholar 

  • Møller-Kristensen, M., Thiel, S., Sjöholm, A., Matsushita, M., & Jensenius, J. C. (2007). Cooperation between MASP-1 and MASP-2 in the generation of C3 convertase through the MBL pathway. International Immunology, 19(2), 141–149.

    Article  CAS  PubMed  Google Scholar 

  • Myhre, O., Utkilen, H., Duale, N., Brunborg, G., & Hofer, T. (2013). Metal dyshomeostasis and inflammation in Alzheimer’s and Parkinson’s diseases: Possible impact of environmental exposures. Oxidative Medicine and Cellular Longevity, 2013, 726954.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Naudé, P. J. W., Nyakas, C., Eiden, L. E., Ait-Ali, D., van der Heide, R., Engelborghs, S., et al. (2012). Lipocalin 2: Novel component of proinflammatory signaling in Alzheimer’s disease. The FASEB Journal, 26(7), 2811–2823.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neufeld, K. M., Kang, N., Bienenstock, J., & Foster, J. A. (2011). Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterology and Motility, 23(3), 255–264.

    Article  CAS  PubMed  Google Scholar 

  • Neugroschl, J., & Wang, S. (2011). Alzheimer’s disease: Diagnosis and treatment across the spectrum of disease severity. Mount Sinai Journal of Medicine, 78(4), 596–612.

    Article  PubMed  Google Scholar 

  • Nielsen, B. S., Borregaard, N., Bundgaard, J. R., Timshel, S., Sehested, M., & Kjeldsen, L. (1996). Induction of NGAL synthesis in epithelial cells of human colorectal neoplasia and inflammatory bowel diseases. Gut, 38, 414–420.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nitti, M., Piras, S., Brondolo, L., Marinari, U. M., Pronzato, M. A., & Furfaro, A. L. (2018). Heme oxygenase 1 in the nervous system: Does it favor neuronal cell survival or induce neurodegeneration? International Journal of Molecular Sciences, 19, 2260. https://doi.org/10.3390/ijms19082260.

    Article  CAS  PubMed Central  Google Scholar 

  • Nzengue, Y., Candéias, S. M., Sauvaigo, S., Douki, T., Favier, A., Rachidi, W., et al. (2011). The toxicity redox mechanisms of cadmium alone or together with copper and zinc homeostasis alteration: Its redox biomarkers. Journal of Trace Elements in Medicine and Biology, 25(3), 171–180.

    Article  CAS  PubMed  Google Scholar 

  • O’Toole, P. W., & Jeffery, I. B. (2015). Gut microbiota and aging. Science, 350(6265), 1214–1215.

    Article  CAS  PubMed  Google Scholar 

  • O’Mahony, S. M., Clarke, G., Borre, Y. E., Dinan, T. G., & Cryan, J. F. (2015). Serotonin, tryptophan metabolism and the brain–gut–microbiome axis. Behavioural Brain Research, 277, 32–48.

    Article  CAS  PubMed  Google Scholar 

  • Park, J.-H., Lee, D.-W., Park, K. S., & Joung, H. J. (2013). Serum trace metal levels in Alzheimer’s disease and normal control groups. American Journal of Alzheimer’s Disease & Other Dementias, 29(1), 76–83.

    Article  Google Scholar 

  • Peng, L., He, Z., Chen, W., Holzman, I. R., & Lin, J. (2007). Effects of butyrate on intestinal barrier function in a Caco-2 cell monolayer model of intestinal barrier. Pediatric Research, 61, 37–41.

    Article  CAS  PubMed  Google Scholar 

  • Peng, L., Yu, Y., Liu, J., Li, S., He, H., Cheng, N., et al. (2015). The chemerin receptor CMKLR1 is a functional receptor for amyloid-β peptide. Journal of Alzheimer’s Disease, 43(1), 227–242. https://doi.org/10.3233/JAD-141227.

    Article  CAS  PubMed  Google Scholar 

  • Percy, M. E., Kruck, T. P. A., Pogue, A. I., & Lukiw, W. J. (2011). Towards the prevention of potential aluminum toxic effects and an effective treatment for Alzheimer’s disease. Journal of Inorganic Biochemistry, 105(11), 1505–1512.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pinto-Sanchez, M. I., Hall, G. B., Ghajar, K., Nardelli, A., Bolino, C., Lau, J. T., et al. (2017). Probiotic Bifidobacterium longum NCC3001 reduces depression scores and alters brain activity: A pilot study in patients with irritable bowel syndrome. Gastroenterology, 153(2), 448–459.

    Article  PubMed  Google Scholar 

  • Psichas, A., Sleeth, M. L., Murphy, K. G., Brooks, L., Bewick, G. A., Hanyaloglu, A. C., et al. (2015). The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. International Journal of Obesity, 39(3), 424–429.

    Article  CAS  PubMed  Google Scholar 

  • Rangaraju, S., Raza, S. A., Li, N. X., Betarbet, R., Dammer, E. B., Duong, D., et al. (2018). Differential phagocytic properties of CD45low microglia and CD45high brain mononuclear phagocytes-activation and age-related effects. Frontiers in Immunology, 9, 405.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ransohoff, R. M. (2016). How neuroinflammation contributes to neurodegeneration. Science, 353(6301), 777–783.

    Article  CAS  PubMed  Google Scholar 

  • Ray, R., Juranek, J. K., & Rai, V. (2016). RAGE axis in neuroinflammation, neurodegeneration and its emerging role in the pathogenesis of amyotrophic lateral sclerosis. Neuroscience and Biobehavioral Reviews, 62, 48–55.

    Article  CAS  PubMed  Google Scholar 

  • Rayaprolu, S., Mullen, B., Baker, M., Lynch, T., Finger, E., Seeley, W. W., et al. (2013). TREM2 in neurodegeneration: Evidence for association of the p.R47H variant with frontotemporal dementia and Parkinson’s disease. Molecular Neurodegeneration, 8, 19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rayner, C. K., & Horowitz, M. (2013). Physiology of the ageing gut. Current Opinion in Clinical Nutrition & Metabolic Care, 16(1), 33–38.

    Article  Google Scholar 

  • Remely, M., Aumueller, E., Jahn, D., Hippe, B., Brath, H., & Haslberger, A. G. (2014a). Microbiota and epigenetic regulation of inflammatory mediators in type 2 diabetes and obesity. Beneficial Microbes, 5(1), 33–43.

    Article  CAS  PubMed  Google Scholar 

  • Remely, M., Aumueller, E., Merold, C., Dworzak, S., Hippe, B., Zanner, J., et al. (2014b). Effects of short chain fatty acid producing bacteria on epigenetic regulation of FFAR3 in type 2 diabetes and obesity. Gene, 537(1), 85–92.

    Article  CAS  PubMed  Google Scholar 

  • Ribet, D., & Cossart, P. (2015). How bacterial pathogens colonize their hosts and invade deeper tissues. Microbes and Infection, 17(3), 173–183.

    Article  CAS  PubMed  Google Scholar 

  • Richardson, K., Fox, C., Maidment, I., Steel, N., Loke, Y. K., Arthur, A., et al. (2018). Anticholinergic drugs and risk of dementia: Case–control study. The BMJ, 361, k1315. https://doi.org/10.1136/bmj.k1315.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ridley, N. J., Draper, B., & Withall, A. (2013). Alcohol-related dementia: An update of the evidence. Alzheimer’s Research & Therapy, 5(1), 3. https://doi.org/10.1186/alzrt157.

    Article  Google Scholar 

  • Rizzi, L., Rosset, I., & Roriz-Cruz, M. (2014). Global epidemiology of dementia: Alzheimer’s and vascular types. BioMed Research International, 2014, 908915.

    Article  PubMed  PubMed Central  Google Scholar 

  • Robinson, L., Tang, E., & Taylor, J.-P. (2015). Dementia: Timely diagnosis and early intervention. The BMJ, 350, h3029.

    Article  PubMed  PubMed Central  Google Scholar 

  • Romijn, A. R., Rucklidge, J. J., Kuijer, R. G., & Frampton, C. (2017). A double-blind, randomized, placebo-controlled trial of Lactobacillus helveticus and Bifidobacterium longum for the symptoms of depression. Australian and New Zealand Journal of Psychiatry, 51(8), 810–821.

    Article  PubMed  Google Scholar 

  • Roos, R. A. (2010). Huntington’s disease: A clinical review. Orphanet Journal of Rare Diseases, 5, 40. https://doi.org/10.1186/1750-1172-5-40.

    Article  PubMed  PubMed Central  Google Scholar 

  • Rossi, M., Johnson, D. W., & Campbell, K. L. (2015). The kidney–gut axis: Implications for nutrition care. Journal of Renal Nutrition, 25(5), 399–403.

    Article  CAS  PubMed  Google Scholar 

  • Russo, R., Cristiano, C., Avagliano, C., De Caro, C., La Rana, G., Raso, G. M., et al. (2017). Gut–brain axis: Role of lipids in the regulation of inflammation, pain and CNS diseases. Current Medicinal Chemistry., 25, 3930–3952. https://doi.org/10.2174/0929867324666170216113756.

    Article  CAS  Google Scholar 

  • Sambamurti, K., Greig, N. H., & Lahiri, D. K. (2002). Advances in the cellular and molecular biology of the beta-amyloid protein in Alzheimer’s disease. NeuroMolecular Medicine, 1(1), 1–31.

    Article  CAS  PubMed  Google Scholar 

  • Sánchez-Villegas, A., Delgado-Rodríguez, M., Alonso, A., Schlatter, J., Lahortiga, F., Serra Majem, L., et al. (2009). Association of the Mediterranean dietary pattern with the incidence of depression: The Seguimiento Universidad de Navarra/University of Navarra follow-up (SUN) cohort. Archives of General Psychiatry, 66(10), 1090–1098.

    Article  PubMed  Google Scholar 

  • Sandahl, T. D., Kelsen, J., Dige, A., Dahlerup, J. F., Agnholt, J., Hvas, C. L., et al. (2014). The lectin pathway of the complement system is downregulated in Crohn’s disease patients who respond to anti-TNF-α therapy. Journal of Crohn’s and Colitis, 8(6), 521–528.

    Article  PubMed  Google Scholar 

  • Sanguinetti, E., Collado, M. C., Marrachelli, V. G., Monleon, D., Selma-Royo, M., Pardo-Tendero, M. M., et al. (2018). Microbiome-metabolome signatures in mice genetically prone to develop dementia, fed a normal or fatty diet. Scientific Report, 8(1), 4907.

    Article  CAS  Google Scholar 

  • Santocchi, E., Guiducci, L., Fulceri, F., Billeci, L., Buzzigoli, E., Apicella, F., et al. (2016). Gut to brain interaction in autism spectrum disorders: A randomized controlled trial on the role of probiotics on clinical, biochemical and neurophysiological parameters. BMC Psychiatry, 16, 183. https://doi.org/10.1186/s12888-016-0887-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saraswati, S., & Sitaraman, R. (2014). Aging and the human gut microbiota-from correlation to causality. Frontiers in Microbiology, 5, 764.

    PubMed  Google Scholar 

  • Saresella, M., La Rosa, F., Piancone, F., Zoppis, M., Marventano, I., Calabrese, E., et al. (2016). The NLRP3 and NLRP1 inflammasomes are activated in Alzheimer’s disease. Molecular Neurodegeneration, 11, 23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Savignac, H. M., Corona, G., Mills, H., Chen, L., Spencer, J. P., Tzortzis, G., et al. (2013). Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-d-aspartate receptor subunits and d-serine. Neurochemistry International, 63(8), 756–764.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sawada, N., Murata, M., Kikuchi, K., Osanai, M., Tobioka, H., Kojima, T., et al. (2003). Tight junctions and human diseases. Medical Electron Microscopy, 36(3), 147–156.

    Article  PubMed  Google Scholar 

  • Schaefer, A. K., Melnyk, J. E., He, Z., Del Rosario, F., & Grimes, C. L. (2018). Pathogen- and microbial- associated molecular patterns (PAMPs/MAMPs) and the innate immune response in Crohn’s disease. In S. Chatterjee, W. Jungraithmayr, & D. Bagchi (Eds.), Immunity and inflammation in health and disease: Emerging roles of nutraceuticals and functional foods in immune support (pp. 175–187). Amsterdam: Academic Press.

    Chapter  Google Scholar 

  • Scheltens, P., Blennow, K., Breteler, M. M., de Strooper, B., Frisoni, G. B., Salloway, S., et al. (2016). Alzheimer’s disease. The Lancet, 388(10043), 505–517.

    Article  CAS  Google Scholar 

  • Schneider, J. A. (2007). Brain microbleeds and cognitive function. Stroke, 38, 1730–1731.

    Article  PubMed  Google Scholar 

  • Serrano-Pozo, A., Frosch, M. P., Masliah, E., & Hyman, B. T. (2011). Neuropathological alterations in Alzheimer disease. Cold Spring Harbor Perspectives in Medicine, 1(1), a006189.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shen, X.-L., Song, N., Du, X.-X., Li, Y., Xie, J.-X., & Jiang, H. (2017). Nesfatin-1 protects dopaminergic neurons against MPP +/MPTP-induced neurotoxicity through the C-Raf–ERK1/2-dependent anti-apoptotic pathway. Scientific Report, 7, 40961.

    Article  CAS  Google Scholar 

  • Shi, S., Wang, G., Zhang, K., Zhang, Z., Liang, K., Li, K., et al. (2017). Expression of S100β protein in patients with vascular dementia after basal ganglia hemorrhage and its clinical significance. Experimental and Therapeutic Medicine, 13(5), 1917–1921.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shprecher, D., Schwalb, J., & Kurlan, R. (2008). Normal pressure hydrocephalus: Diagnosis and treatment. Current Neurology and Neuroscience Reports, 8(5), 371–376.

    Article  PubMed  PubMed Central  Google Scholar 

  • Skandalis, S. S., Dobra, K., Götte, M., Karousou, E., & Misra, S. (2015). Impact of extracellular matrix on cellular behavior: A source of molecular targets in disease. BioMed Research International, 2015, 482879.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sochocka, M., Zwolińska, K., & Leszek, J. (2017). The infectious etiology of Alzheimer’s disease. Current Neuropharmacology, 15(7), 996–1009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soenen, S., Rayner, C. K., Jones, K. L., & Horowitz, M. (2016). The ageing gastrointestinal tract. Current Opinion in Clinical Nutrition & Metabolic Care, 19(1), 12–18.

    Article  Google Scholar 

  • Song, J., & Kim, O. Y. (2018). Perspectives in lipocalin-2: Emerging biomarker for medical diagnosis and prognosis for Alzheimer’s disease. Clinical Nutrition Research, 7(1), 1–10.

    Article  PubMed  PubMed Central  Google Scholar 

  • Srikanth, V., Maczurek, A., Phan, T., Steele, M., Westcott, B., Juskiw, D., et al. (2011). Advanced glycation endproducts and their receptor RAGE in Alzheimer’s disease. Neurobiology of Aging, 32(5), 763–777.

    Article  CAS  PubMed  Google Scholar 

  • Stanga, S., Lanni, C., Govoni, S., Uberti, D., D’Orazi, G., & Racchi, M. (2010). Unfolded p53 in the pathogenesis of Alzheimer’s disease: Is HIPK2 the link? Aging (Albany, NY), 2(9), 545–554.

    Article  CAS  Google Scholar 

  • Starr, J. M., & Whalley, L. J. (1994). Drug-induced dementia: Incidence, management and prevention. Drug Safety, 11(5), 310–317.

    Article  CAS  PubMed  Google Scholar 

  • Streit, W. J., Mrak, R. E., & Griffin, W. S. T. (2004). Microglia and neuroinflammation: A pathological perspective. Journal of Neuroinflammation, 1, 14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stuart, M. J., Corrigan, F., & Baune, B. T. (2014). Knockout of CXCR227 increases the population of immature neural cells and decreases proliferation in the hippocampal dentate gyrus. Journal of Neuroinflammation, 11, 31. https://doi.org/10.1186/1742-2094-11-31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sudo, N., Chida, Y., Aiba, Y., Sonoda, J., Oyama, N., Yu, X. N., et al. (2004). Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. Journal of Physiology, 558(Pt 1), 263–275.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tahara, Y., Yamazaki, M., Sukigara, H., Motohashi, H., Sasaki, H., Miyakawa, H., et al. (2018). Gut microbiota-derived short chain fatty acids induce circadian clock entrainment in mouse peripheral tissue. Scientific Report, 8(1), 1395.

    Article  CAS  Google Scholar 

  • Takeuchi, O., & Akira, S. (2010). Pattern recognition receptors and inflammation. Cell, 140(6), 805–820.

    Article  CAS  PubMed  Google Scholar 

  • Takeuchi, M., & Yamagishi, S. (2008). Possible involvement of advanced glycation end-products (AGEs) in the pathogenesis of Alzheimer’s disease. Current Pharmaceutical Design, 14(10), 973–978.

    Article  CAS  PubMed  Google Scholar 

  • Tan, J., McKenzie, C., Potamitis, M., Thorburn, A. N., Mackay, C. R., & Macia, L. (2014). The role of short-chain fatty acids in health and disease. Advances in Immunology, 121, 91–119.

    Article  CAS  PubMed  Google Scholar 

  • Tanaka, S., & Nagashima, H. (2018). Establishment of an Alzheimer’s disease model with latent herpesvirus infection using PS2 and Tg2576 double transgenic mice. Experimental Animals, 67(2), 185–192.

    Article  CAS  PubMed  Google Scholar 

  • Tang, S.-C., Yang, K.-C., Hu, C.-J., Chiou, H.-Y., Wu, C. C., & Jeng, J.-S. (2017). Elevated plasma level of soluble form of RAGE in ischemic stroke patients with dementia. NeuroMolecular Medicine, 19(4), 579–583.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Taskesen, E., Mishra, A., van der Sluis, S., International FTD-Genomics Consortium, Ferrari, R., Veldink, J. H., et al. (2017). Susceptible genes and disease mechanisms identified in frontotemporal dementia and frontotemporal dementia with amyotrophic lateral sclerosis by DNA-methylation and GWAS. Scientific Report, 7, 8899.

    Article  CAS  Google Scholar 

  • Thakur, A. K., Shakya, A., Husain, G. M., Emerald, M., & Kumar, V. (2014). Gut-microbiota and mental health: Current and future perspectives. Journal of Pharmacology & Clinical Toxicology, 2(1), 1016.

    Google Scholar 

  • Thelen, T., Hao, Y., Medeiros, A. I., Curtis, J. L., Serezani, C. H., Kobzik, L., et al. (2010). The class A scavenger receptor, macrophage receptor with collagenous structure, is the major phagocytic receptor for Clostridium sordellii expressed by human decidual macrophages. Journal of Immunology, 185(7), 4328–4335.

    Article  CAS  Google Scholar 

  • Theocharis, A. D., Skandalis, S. S., Gialeli, C., & Karamanos, N. K. (2016). Extracellular matrix structure. Advanced Drug Delivery Reviews, 97, 4–27.

    Article  CAS  PubMed  Google Scholar 

  • Thome, J., Kornhuber, J., Münch, G., Schinzel, R., Taneli, Y., Zielke, B., et al. (1996). New hypothesis on etiopathogenesis of Alzheimer syndrome. Advanced glycation end products (AGEs). Nervenarzt, 67(11), 924–929.

    Article  CAS  PubMed  Google Scholar 

  • Thorsvik, S., Bakke, I., van Beelen, Granlund A., Røyset, E. S., Jan Damås, K., Østvik, A. E., et al. (2018). Expression of neutrophil gelatinase-associated lipocalin (NGAL) in the gut in Crohn’s disease. Cell and Tissue Research, 374(2), 339–348.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tóbon-Velasco, J. C., Cuevas, E., & Torres-Ramos, M. A. (2014). Receptor for AGEs (RAGE) as mediator of NF-kB pathway activation in neuroinflammation and oxidative stress. CNS & Neurological Disorders: Drug Targets, 13(9), 1615–1626.

    Article  CAS  Google Scholar 

  • Tong, X. K., & Hamel, E. (1999). Regional cholinergic denervation of cortical microvessels and nitric oxide synthase-containing neurons in Alzheimer’s disease. Neuroscience, 92(1), 163–175.

    Article  CAS  PubMed  Google Scholar 

  • Uribarri, J., Cai, W., Peppa, M., Goodman, S., Ferrucci, L., Striker, G., et al. (2007). Circulating glycotoxins and dietary advanced glycation endproducts: Two links to inflammatory response, oxidative stress, and aging. Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 62(4), 427–433.

    Article  Google Scholar 

  • Valko, M., Morris, H., & Cronin, M. T. (2005). Metals, toxicity and oxidative stress. Current Medicinal Chemistry, 12(10), 1161–1208.

    Article  CAS  PubMed  Google Scholar 

  • Varadarajan, S., Yatin, S., Aksenova, M., & Butterfield, D. A. (2000). Review: Alzheimer’s amyloid beta-peptide-associated free radical oxidative stress and neurotoxicity. Journal of Structural Biology, 130(2–3), 184–208.

    Article  CAS  PubMed  Google Scholar 

  • Veerappan, C. S., Sleiman, S., & Coppola, G. (2013). Epigenetics of Alzheimer’s disease and frontotemporal dementia. Neurotherapeutics, 10(4), 709–721.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Venegas, C., & Heneka, M. T. (2017). Danger-associated molecular patterns in Alzheimer’s disease. Journal of Leukocyte Biology, 101(1), 87–98.

    Article  CAS  PubMed  Google Scholar 

  • Vogt, N. M., Kerby, R. L., Dill-McFarland, K. A., Harding, S. J., Merluzzi, A. P., Johnson, S. C., et al. (2017). Gut microbiome alterations in Alzheimer’s disease. Scientific Report, 7, 13537.

    Article  CAS  Google Scholar 

  • Walker, D. G., & Lue, L.-F. (2015). Immune phenotypes of microglia in human neurodegenerative disease: Challenges to detecting microglial polarization in human brains. Alzheimer’s Research & Therapy, 7(1), 56. https://doi.org/10.1186/s13195-015-0139-9.

    Article  CAS  Google Scholar 

  • Wallace, C. J. K., & Milev, R. (2017). The effects of probiotics on depressive symptoms in humans: A systematic review. Annals of General Psychiatry, 16, 14. https://doi.org/10.1186/s12991-017-0138-2.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang, H., Lee, I.-S., Braun, C., & Enck, P. (2016a). Effect of probiotics on central nervous system functions in animals and humans: A systematic review. Journal of Neurogastroenterology and Motility, 22(4), 589–605.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang, Y., Ulland, T. K., Ulrich, J. D., Song, W., Tzaferis, J. A., Hole, J. T., et al. (2016b). TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques. Journal of Experimental Medicine, 213(5), 667–675.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weber, C. R., Nalle, S. C., Tretiakova, M., Rubin, D. T., & Turner, J. R. (2008). Claudin-1 and claudin-2 expression is elevated in inflammatory bowel disease and may contribute to early neoplastic transformation. Laboratory Investigation, 88(10), 1110–1120.

    Article  CAS  PubMed  Google Scholar 

  • Welcome, M. O. (2018). Gastrointestinal physiology: Development, principles and mechanism of regulation. Cham: Springer.

    Book  Google Scholar 

  • Wenning, G., Litvan, I., Jankovic, J., Granata, R., Mangone, C. A., McKee, A., et al. (1998). Natural history and survival of 14 patients with corticobasal degeneration confirmed at postmortem examination. Journal of Neurology, Neurosurgery and Psychiatry, 64, 184–189.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Westfall, S., Lomis, N., Kahouli, I., Dia, S. Y., Singh, S. P., & Prakash, S. (2017). Microbiome, probiotics and neurodegenerative diseases: Deciphering the gut brain axis. Cellular and Molecular Life Sciences, 74(20), 3769–3787.

    Article  CAS  PubMed  Google Scholar 

  • Williams, C.-A., Lin, Y., Maynard, A., & Cheng, S.-Y. (2013). Involvement of NF kappa B in potentiated effect of Mn-containing dithiocarbamates on MPP + induced cell death. Cellular and Molecular Neurobiology, 33(6), 815–823.

    Article  CAS  PubMed  Google Scholar 

  • Wimo, A., Jonsson, L., & Winblad, B. (2006). An estimate of the worldwide prevalence and direct costs of dementia in 2003. Dementia and Geriatric Cognitive Disorders, 21(3), 175–181.

    Article  CAS  PubMed  Google Scholar 

  • Wimo, A., Winblad, B., & Jönsson, L. (2010). The worldwide societal costs of dementia: Estimates for 2009. Alzheimer’s & Dementia, 6(2), 98–103.

    Article  Google Scholar 

  • Wing, M. R., Patel, S. S., Ramezani, A., & Raj, D. S. (2016). Gut microbiome in chronic kidney disease. Experimental Physiology, 101(4), 471–477.

    Article  CAS  PubMed  Google Scholar 

  • Woollacott, I. O. C., Nicholas, J. M., Heslegrave, A., Heller, C., Foiani, M. S., Dick, K. M., et al. (2018). Cerebrospinal fluid soluble TREM2 levels in frontotemporal dementia differ by genetic and pathological subgroup. Alzheimer’s Research & Therapy, 10(1), 79. https://doi.org/10.1186/s13195-018-0405-8.

    Article  CAS  Google Scholar 

  • Wozniak, M. A., Mee, A. P., & Itzhaki, R. F. (2009). Herpes simplex virus type 1 DNA is located within Alzheimer’s disease amyloid plaques. Journal of Pathology, 217(1), 131–138.

    Article  CAS  PubMed  Google Scholar 

  • Xiong, C., Liu, J., Lin, D., Zhang, J., Terrando, N., & Wu, A. (2018). Complement activation contributes to perioperative neurocognitive disorders in mice. Journal of Neuroinflammation, 15(1), 254. https://doi.org/10.1186/s12974-018-1292-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu, Y., Yan, J., Zhou, P., Li, J., Gao, H., Xia, Y., et al. (2012). Neurotransmitter receptors and cognitive dysfunction in Alzheimer’s disease and Parkinson’s disease. Progress in Neurobiology, 97(1), 1–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yin, Z., Raj, D., Saiepour, N., Van Dam, D., Brouwer, N., Holtman, I. R., et al. (2017). Immune hyperreactivity of Aβ plaque-associated microglia in Alzheimer’s disease. Neurobiology of Aging, 55, 115–122.

    Article  CAS  PubMed  Google Scholar 

  • Yoshiike, Y., Kimura, T., Yamashita, S., Furudate, H., Mizoroki, T., Murayama, M., et al. (2008). GABA(A) receptor-mediated acceleration of aging-associated memory decline in APP/PS1 mice and its pharmacological treatment by picrotoxin. PLoS ONE, 3(8), e3029.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu, Y., & Ye, R. D. (2015). Microglial Aβ receptors in Alzheimer’s disease. Cellular and Molecular Neurobiology, 35(1), 71–83.

    Article  CAS  PubMed  Google Scholar 

  • Zamboni, G., Grafman, J., Krueger, F., Knutson, K. M., & Huey, E. D. (2010). Anosognosia for behavioral disturbances in frontotemporal dementia and corticobasal syndrome: A voxel-based morphometry study. Dementia and Geriatric Cognitive Disorders, 29(1), 88–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zeissig, S., Bürgel, N., Günzel, D., Richter, J., Mankertz, J., Wahnschaffe, U., et al. (2007). Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn’s disease. Gut, 56(1), 61–72.

    Article  CAS  PubMed  Google Scholar 

  • Zhao, H., Shi, Y., Luo, X., Peng, L., Yang, Y., & Zou, L. (2017). The effect of fecal microbiota transplantation on a child with tourette syndrome. Case Reports in Medicine, 2017, 6165239. https://doi.org/10.1155/2017/6165239.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zheng, P., Zeng, B., Zhou, C., Liu, M., Fang, Z., Xu, X., et al. (2016). Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism. Molecular Psychiatry, 21(6), 786–796.

    Article  CAS  PubMed  Google Scholar 

  • Zhu, C. S., Grandhi, R., Patterson, T. T., & Nicholson, S. E. (2018). A review of traumatic brain injury and the gut microbiome: Insights into novel mechanisms of secondary brain injury and promising targets for neuroprotection. Brain Science, 8(6), 113.

    Article  CAS  Google Scholar 

  • Zihni, C., Mills, C., Matter, K., & Balda, M. S. (2016). Tight junctions: From simple barriers to multifunctional molecular gates. Nature Reviews Molecular Cell Biology, 17, 564–580.

    Article  CAS  PubMed  Google Scholar 

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Welcome, M.O. Gut Microbiota Disorder, Gut Epithelial and Blood–Brain Barrier Dysfunctions in Etiopathogenesis of Dementia: Molecular Mechanisms and Signaling Pathways. Neuromol Med 21, 205–226 (2019). https://doi.org/10.1007/s12017-019-08547-5

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