Abstract
Alzheimer’s disease (AD) represents one of the main forms of dementia that afflicts our society. The expression of several genes has been associated with disease development. Despite this, the number of genes known to be capable of discriminating between AD patients according to sex remains deficient. In our study, we performed a transcriptomes meta-analysis on a large court of brains of healthy control subjects (n = 2139) (NDHC) and brains of AD patients (n = 1170). Our aim was to verify the brain expression levels of CHI3L2 and its correlation with genes associated with microglia-mediated neuroinflammation (IBA1), alteration of the blood–brain barrier (PECAM1), and neuronal damage (CALB1). We showed that the CHI3L2, IBA1, PECAM1, and CALB1 expression levels were modulated in the brains of patients with AD compared to NDHC subjects. Furthermore, both in NDHC and in AD patient’s brains, the CHI3L2 expression levels were directly correlated with IBA1 and PECAM1 and inversely with CALB1. Additionally, the expression levels of CHI3L2, PECAM1, and CALB1 but not of IBA1 were sex-depended. By stratifying the samples according to age and sex, correlation differences emerged between the expression levels of CHI3L2, IBA1, PECAM1, and CALB1 and the age of NDHC subjects and AD patients. CHI3L2 represents a promising gene potentially involved in the key processes underlying Alzheimer’s disease. Its expression in the brains of sex-conditioned AD patients opens up new possible sex therapeutic strategies aimed at controlling imbalance in disease progression.
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Abbreviations
- MD:
-
microarray datasets
- AD:
-
Alzheimer’s disease
- PD:
-
Parkinson disease
- MS:
-
Multiple sclerosis
- MeV:
-
MultiExperiment Viewer
- FDR:
-
False discovery rate
- ALS:
-
Amyotrophic lateral sclerosis
- CNS:
-
Central nervous system
- AIF1:
-
Allograft inflammatory factor-1
- IBA1:
-
Ionized calcium-binding adapter molecule 1
- PECAM-1:
-
Platelet endothelial cell adhesion molecule
- CD31:
-
Cluster of differentiation 31
- CALB1:
-
Calbindin 1
- BBB:
-
Blood–brain barrier
References
Berchtold NC, Cribbs DH, Coleman PD, Rogers J, Head E, Kim R, Beach T, Miller C, Troncoso J, Trojanowski JQ, Zielke HR, Cotman CW (2008) Gene expression changes in the course of normal brain aging are sexually dimorphic. Proc Natl Acad Sci U S A 105(40):15605–15610
Berchtold NC, Coleman PD, Cribbs DH, Rogers J, Gillen DL, Cotman CW (2013) Synaptic genes are extensively downregulated across multiple brain regions in normal human aging and Alzheimer's disease. Neurobiol Aging 34(6):1653–1661
Blalock EM, Buechel HM, Popovic J, Geddes JW, Landfield PW (2011) Microarray analyses of laser-captured hippocampus reveal distinct gray and white matter signatures associated with incipient Alzheimer's disease. J Chem Neuroanat 42(2):118–126
Blennow K, de Leon MJ, Zetterberg H (2006) Alzheimer's disease. Lancet 368(9533):387–403
Care MA, Barrans S, Worrillow L, Jack A, Westhead DR, Tooze RM (2013) A microarray platform-independent classification tool for cell of origin class allows comparative analysis of gene expression in diffuse large B-cell lymphoma. PLoS One 8(2):e55895
Cheadle C, Vawter MP, Freed WJ, Becker KG (2003a) Analysis of microarray data using Z score transformation. J Mol Diagn 5(2):73–81
Cheadle C, Cho-Chung YS, Becker KG, Vawter MP (2003b) Application of z-score transformation to Affymetrix data. Appl Bioinforma 2(4):209–217
Chen QR, Song YK, Wei JS, Bilke S, Asgharzadeh S, Seeger RC, Khan J (2008) An integrated cross-platform prognosis study on neuroblastoma patients. Genomics 92(4):195–203
Chen C, Meng Q, Xia Y, Ding C, Wang L, Dai R, Cheng L, Gunaratne P, Gibbs RA, Min S, Coarfa C, Reid JG, Zhang C, Jiao C, Jiang Y, Giase G, Thomas A, Fitzgerald D, Brunetti T, Shieh A, Xia C, Wang Y, Wang Y, Badner JA, Gershon ES, White KP, Liu C (2018) The transcription factor POU3F2 regulates a gene coexpression network in brain tissue from patients with psychiatric disorders. Sci translat Med 10(472):eaat8178
Davis S, Meltzer PS (2007) GEOquery: a bridge between the gene expression omnibus (GEO) and BioConductor. Bioinformatics 23(14):1846–1847
Del Galdo F, Maul GG, Jimenez SA, Artlett CM (2006) Expression of allograft inflammatory factor 1 in tissues from patients with systemic sclerosis and in vitro differential expression of its isoforms in response to transforming growth factor beta. Arthritis Rheum 54(8):2616–2625
Di Rosa M, Malaguarnera L (2016) Chitinase 3 Like-1: an emerging molecule involved in diabetes and diabetic complications. Pathobiology 83(5):228–242
Di Rosa M, Zambito AM, Marsullo AR, Li Volti G, Malaguarnera L (2009) Prolactin induces chitotriosidase expression in human macrophages through PTK, PI3-K, and MAPK pathways. J Cell Biochem 107(5):881–889
Di Rosa M, Malaguarnera G, De Gregorio C, Drago F, Malaguarnera L (2013) Evaluation of CHI3L-1 and CHIT-1 expression in differentiated and polarized macrophages. Inflammation 36(2):482–492
Di Rosa M, Tibullo D, Vecchio M, Nunnari G, Saccone S, Di Raimondo F, Malaguarnera L (2014a) Determination of chitinases family during osteoclastogenesis. Bone 61:55–63
Di Rosa M, Szychlinska MA, Tibullo D, Malaguarnera L, Musumeci G (2014b) Expression of CHI3L1 and CHIT1 in osteoarthritic rat cartilage model. A morphological study. Eur J Histochem 58(3):2423
Di Rosa M, Sanfilippo C, Libra M, Musumeci G, Malaguarnera L (2015) Different pediatric brain tumors are associated with different gene expression profiling. Acta Histochem 117(4–5):477–485
Di Rosa M, Tibullo D, Saccone S, Distefano G, Basile MS, Di Raimondo F, Malaguarnera L (2016) CHI3L1 nuclear localization in monocyte derived dendritic cells. Immunobiology 221(2):347–356
Durrenberger PF, Fernando FS, Kashefi SN, Bonnert TP, Seilhean D, Nait-Oumesmar B, Schmitt A, Gebicke-Haerter PJ, Falkai P, Grunblatt E, Palkovits M, Arzberger T, Kretzschmar H, Dexter DT, Reynolds R (2015) Common mechanisms in neurodegeneration and neuroinflammation: a BrainNet Europe gene expression microarray study. J Neural Transm 122(7):1055–1068
Fairless R, Williams SK, Diem R (2019) Calcium-binding proteins as determinants of central nervous system neuronal vulnerability to disease. Int J Mol Sci 20(9):2146
Feng C, Wu J, Yang F, Qiu M, Hu S, Guo S, Wu J, Ying X, Wang J (2018) Expression of Bcl-2 is a favorable prognostic biomarker in lung squamous cell carcinoma. Oncol Lett 15(5):6925–6930
Frankel R, Tornquist M, Meisl G, Hansson O, Andreasson U, Zetterberg H, Blennow K, Frohm B, Cedervall T, Knowles TPJ, Leiding T, Linse S (2019) Autocatalytic amplification of Alzheimer-associated Abeta42 peptide aggregation in human cerebrospinal fluid. Communications Biol 2(1):365
French L, Ma T, Oh H, Tseng GC, Sibille E (2017) Age-related gene expression in the frontal cortex suggests synaptic function changes in specific inhibitory neuron subtypes. Front Aging Neurosci 9:162
Gelman BB, Chen T, Lisinicchia JG, Soukup VM, Carmical JR, Starkey JM, Masliah E, Commins DL, Brandt D, Grant I, Singer EJ, Levine AJ, Miller J, Winkler JM, Fox HS, Luxon BA, Morgello S, National Neuro ATC (2012) The National NeuroAIDS tissue consortium brain gene array: two types of HIV-associated neurocognitive impairment. PLoS One 7(9):e46178
Gibbs JR, van der Brug MP, Hernandez DG, Traynor BJ, Nalls MA, Lai SL, Arepalli S, Dillman A, Rafferty IP, Troncoso J, Johnson R, Zielke HR, Ferrucci L, Longo DL, Cookson MR, Singleton AB (2010) Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain. PLoS Genet 6(5):e1000952
Giorgetti E, Panesar M, Zhang Y, Joller S, Ronco M, Obrecht M, Lambert C, Accart N, Beckmann N, Doelemeyer A, Perrot L, Fruh I, Mueller M, Pierrel E, Summermatter S, Bidinosti M, Shimshek DR, Brachat S, Nash M (2019) Modulation of microglia by voluntary exercise or CSF1R inhibition prevents age-related loss of functional motor units. Cell Rep 29(6):1539–1554 e7
Gitler AD, Dhillon P, Shorter J (2017) Neurodegenerative disease: models, mechanisms, and a new hope. Disease Models Mechan 10(5):499–502
Hagenauer MH, Schulmann A, Li JZ, Vawter MP, Walsh DM, Thompson RC, Turner CA, Bunney WE, Myers RM, Barchas JD, Schatzberg AF, Watson SJ, Akil H (2018) Inference of cell type content from human brain transcriptomic datasets illuminates the effects of age, manner of death, dissection, and psychiatric diagnosis. PLoS One 13(7):e0200003
Hernandez DG, Nalls MA, Moore M, Chong S, Dillman A, Trabzuni D, Gibbs JR, Ryten M, Arepalli S, Weale ME, Zonderman AB, Troncoso J, O'Brien R, Walker R, Smith C, Bandinelli S, Traynor BJ, Hardy J, Singleton AB, Cookson MR (2012) Integration of GWAS SNPs and tissue specific expression profiling reveal discrete eQTLs for human traits in blood and brain. Neurobiol Dis 47(1):20–28
Hochstrasser T, Weiss E, Marksteiner J, Humpel C (2010) Soluble cell adhesion molecules in monocytes of Alzheimer's disease and mild cognitive impairment. Exp Gerontol 45(1):70–74
Hokama M, Oka S, Leon J, Ninomiya T, Honda H, Sasaki K, Iwaki T, Ohara T, Sasaki T, LaFerla FM, Kiyohara Y, Nakabeppu Y (2014) Altered expression of diabetes-related genes in Alzheimer's disease brains: the Hisayama study. Cereb Cortex 24(9):2476–2488
Hou Y, Dan X, Babbar M, Wei Y, Hasselbalch SG, Croteau DL, Bohr VA (2019) Ageing as a risk factor for neurodegenerative disease. Nat Rev Neurol 15(10):565–581
Kalinowska A, Losy J (2006) PECAM-1, a key player in neuroinflammation. Eur J Neurol 13(12):1284–1290
Kang HJ, Kawasawa YI, Cheng F, Zhu Y, Xu X, Li M, Sousa AM, Pletikos M, Meyer KA, Sedmak G, Guennel T, Shin Y, Johnson MB, Krsnik Z, Mayer S, Fertuzinhos S, Umlauf S, Lisgo SN, Vortmeyer A, Weinberger DR, Mane S, Hyde TM, Huttner A, Reimers M, Kleinman JE, Sestan N (2011) Spatio-temporal transcriptome of the human brain. Nature 478(7370):483–489
Kang C, Huo Y, Xin L, Tian B, Yu B (2019) Feature selection and tumor classification for microarray data using relaxed lasso and generalized multi-class support vector machine. J Theor Biol 463:77–91
Kaya I, Brinet D, Michno W, Baskurt M, Zetterberg H, Blenow K, Hanrieder J (2017) Novel Trimodal MALDI imaging mass spectrometry (IMS3) at 10 mum reveals spatial lipid and peptide correlates implicated in Abeta plaque pathology in Alzheimer's disease. ACS Chem Neurosci 8(12):2778–2790
Kiyama H, Seto-Ohshima A, Emson PC (1990) Calbindin D28K as a marker for the degeneration of the striatonigral pathway in Huntington's disease. Brain Res 525(2):209–214
Kook SY, Jeong H, Kang MJ, Park R, Shin HJ, Han SH, Son SM, Song H, Baik SH, Moon M, Yi EC, Hwang D, Mook-Jung I (2014) Crucial role of calbindin-D28k in the pathogenesis of Alzheimer's disease mouse model. Cell Death Differ 21(10):1575–1587
Kumaran R, Cookson MR (2015) Pathways to parkinsonism redux: convergent pathobiological mechanisms in genetics of Parkinson's disease. Hum Mol Genet 24(R1):R32–R44
Kwak EJ, Hong JY, Kim MN, Kim SY, Kim SH, Park CO, Kim KW, Lee CG, Elias JA, Jee HM, Sohn MH (2019) Chitinase 3-like 1 drives allergic skin inflammation via Th2 immunity and M2 macrophage activation. Clin Exp Allergy: J British Soci Allergy Clin Immunol 49(11):1464–1474
Le Cao KA, Rohart F, McHugh L, Korn O, Wells CA (2014) YuGene: a simple approach to scale gene expression data derived from different platforms for integrated analyses. Genomics 103(4):239–251
Li JZ, Bunney BG, Meng F, Hagenauer MH, Walsh DM, Vawter MP, Evans SJ, Choudary PV, Cartagena P, Barchas JD, Schatzberg AF, Jones EG, Myers RM, Watson SJ Jr, Akil H, Bunney WE (2013) Circadian patterns of gene expression in the human brain and disruption in major depressive disorder. Proc Natl Acad Sci U S A 110(24):9950–9955
Liang WS, Dunckley T, Beach TG, Grover A, Mastroeni D, Walker DG, Caselli RJ, Kukull WA, McKeel D, Morris JC, Hulette C, Schmechel D, Alexander GE, Reiman EM, Rogers J, Stephan DA (2007) Gene expression profiles in anatomically and functionally distinct regions of the normal aged human brain. Physiol Genomics 28(3):311–322
Limaos EA, Borges DR, Souza-Pinto JC, Gordon AH, Prado JL (1981) Acute turpentine inflammation and kinin release in rat-paw thermic oedema. Br J Exp Pathol 62(6):591–594
Litviakov N, Tsyganov M, Larionova I, Ibragimova M, Deryusheva I, Kazantseva P, Slonimskaya E, Frolova I, Choinzonov E, Cherdyntseva N, Kzhyshkowska J (2018) Expression of M2 macrophage markers YKL-39 and CCL18 in breast cancer is associated with the effect of neoadjuvant chemotherapy. Cancer Chemother Pharmacol 82(1):99–109
Malaguarnera L, Imbesi R, Di Rosa M, Scuto A, Castrogiovanni P, Messina A, Sanfilippo S (2005) Action of prolactin, IFN-gamma, TNF-alpha and LPS on heme oxygenase-1 expression and VEGF release in human monocytes/macrophages. Int Immunopharmacol 5(9):1458–1469
Masliah E, Ge N, Achim CL, Wiley CA (1995) Differential vulnerability of calbindin-immunoreactive neurons in HIV encephalitis. J Neuropathol Exp Neurol 54(3):350–357
Mazure CM, Swendsen J (2016) Sex differences in Alzheimer's disease and other dementias. Lancet Neurol 15(5):451–452
Mehmood R, El-Ashram S, Bie R, Dawood H, Kos A (2017) Clustering by fast search and merge of local density peaks for gene expression microarray data. Sci Rep 7:45602
Mollgaard M, Degn M, Sellebjerg F, Frederiksen JL, Modvig S (2016) Cerebrospinal fluid chitinase-3-like 2 and chitotriosidase are potential prognostic biomarkers in early multiple sclerosis. Eur J Neurol 23(5):898–905
Moreno-Rodriguez M, Perez SE, Nadeem M, Malek-Ahmadi M, Mufson EJ (2020) Frontal cortex chitinase and pentraxin neuroinflammatory alterations during the progression of Alzheimer's disease. J Neuroinflammation 17(1):58
Nakagawa S, Castro V, Toborek M (2012) Infection of human pericytes by HIV-1 disrupts the integrity of the blood-brain barrier. J Cell Mol Med 16(12):2950–2957
Narayanan M, Huynh JL, Wang K, Yang X, Yoo S, McElwee J, Zhang B, Zhang C, Lamb JR, Xie T, Suver C, Molony C, Melquist S, Johnson AD, Fan G, Stone DJ, Schadt EE, Casaccia P, Emilsson V, Zhu J (2014) Common dysregulation network in the human prefrontal cortex underlies two neurodegenerative diseases. Mol Syst Biol 10:743
Patel H, Hodges AK, Curtis C, Lee SH, Troakes C, Dobson RJB, Newhouse SJ (2019) Transcriptomic analysis of probable asymptomatic and symptomatic alzheimer brains. Brain Behav Immun 80:644–656
Privratsky JR, Newman PJ (2014) PECAM-1: regulator of endothelial junctional integrity. Cell Tissue Res 355(3):607–619
Qiu QC, Wang L, Jin SS, Liu GF, Liu J, Ma L, Mao RF, Ma YY, Zhao N, Chen M, Lin BY (2018) CHI3L1 promotes tumor progression by activating TGF-beta signaling pathway in hepatocellular carcinoma. Sci Rep 8(1):15029
Reddy TB, Riley R, Wymore F, Montgomery P, DeCaprio D, Engels R, Gellesch M, Hubble J, Jen D, Jin H, Koehrsen M, Larson L, Mao M, Nitzberg M, Sisk P, Stolte C, Weiner B, White J, Zachariah ZK, Sherlock G, Galagan JE, Ball CA, Schoolnik GK (2009) TB database: an integrated platform for tuberculosis research. Nucleic Acids Res 37(Database issue):D499–D508
Reus GZ, Silva RH, de Moura AB, Presa JF, Abelaira HM, Abatti M, Vieira A, Pescador B, Michels M, Ignacio ZM, Dal-Pizzol F, Quevedo J (2019) Early maternal deprivation induces microglial activation, alters glial fibrillary acidic protein immunoreactivity and Indoleamine 2,3-dioxygenase during the development of offspring rats. Mol Neurobiol 56(2):1096–1108
Ryan MM, Lockstone HE, Huffaker SJ, Wayland MT, Webster MJ, Bahn S (2006) Gene expression analysis of bipolar disorder reveals downregulation of the ubiquitin cycle and alterations in synaptic genes. Mol Psychiatry 11(10):965–978
Sanfilippo C, Malaguarnera L, Di Rosa M (2016) Chitinase expression in Alzheimer's disease and non-demented brains regions. J Neurol Sci 369:242–249
Sanfilippo C, Longo A, Lazzara F, Cambria D, Distefano G, Palumbo M, Cantarella A, Malaguarnera L, Di Rosa M (2017a) CHI3L1 and CHI3L2 overexpression in motor cortex and spinal cord of sALS patients. Mol Cell Neurosci 85:162–169
Sanfilippo C, Nunnari G, Calcagno A, Malaguarnera L, Blennow K, Zetterberg H, Di Rosa M (2017b) The chitinases expression is related to simian immunodeficiency virus encephalitis (SIVE) and in HIV encephalitis (HIVE). Virus Res 227:220–230
Sanfilippo C, Castrogiovanni P, Imbesi R, Kazakowa M, Musumeci G, Blennow K, Zetterberg H, Di Rosa M (2019a) Sex difference in CHI3L1 expression levels in human brain aging and in Alzheimer's disease. Brain Res 1720:146305
Sanfilippo C, Castrogiovanni P, Imbesi R, Tibullo D, Li Volti G, Barbagallo I, Vicario N, Musumeci G, Di Rosa M (2019b) Middle-aged healthy women and Alzheimer's disease patients present an overlapping of brain cell transcriptional profile. Neuroscience 406:333–344
Scarpino M, Pinzone MR, Di Rosa M, Madeddu G, Foca E, Martellotta F, Schioppa O, Ceccarelli G, Celesia BM, d'Ettorre G, Vullo V, Berretta S, Cacopardo B, Nunnari G (2013) Kidney disease in HIV-infected patients. Eur Rev Med Pharmacol Sci 17(19):2660–2667
Schwab JM, Frei E, Klusman I, Schnell L, Schwab ME, Schluesener HJ (2001) AIF-1 expression defines a proliferating and alert microglial/macrophage phenotype following spinal cord injury in rats. J Neuroimmunol 119(2):214–222
Sjostedt E, Zhong W, Fagerberg L, Karlsson M, Mitsios N, Adori C, Oksvold P, Edfors F, Limiszewska A, Hikmet F, Huang J, Du Y, Lin L, Dong Z, Yang L, Liu X, Jiang H, Xu X, Wang J, Yang H, Bolund L, Mardinoglu A, Zhang C, von Feilitzen K, Lindskog C, Ponten F, Luo Y, Hokfelt T, Uhlen M, Mulder J (2020) An atlas of the protein-coding genes in the human, pig, and mouse brain. Science 367(6482):eaay5947
Smyth GY (2004) Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 3:Article3
Spittau B (2017) Aging microglia-phenotypes, functions and implications for age-related neurodegenerative diseases. Front Aging Neurosci 9:194
Szychlinska MA, Trovato FM, Di Rosa M, Malaguarnera L, Puzzo L, Leonardi R, Castrogiovanni P, Musumeci G (2016) Co-expression and co-localization of cartilage glycoproteins CHI3L1 and Lubricin in osteoarthritic cartilage: morphological, Immunohistochemical and gene expression profiles. Int J Mol Sci 17(3):359
Box GEP, Tiao GC (1992) Bayesian inference in statistical analysis. Wiley, New York
Trabzuni D, Ramasamy A, Imran S, Walker R, Smith C, Weale ME, Hardy J, Ryten M, North American Brain Expression Consortium (2013) Widespread sex differences in gene expression and splicing in the adult human brain. Nat Commun 4:2771
Wang J, Coombes KR, Highsmith WE, Keating MJ, Abruzzo LV (2004) Differences in gene expression between B-cell chronic lymphocytic leukemia and normal B cells: a meta-analysis of three microarray studies. Bioinformatics 20(17):3166–3178
Wang M, Roussos P, McKenzie A, Zhou X, Kajiwara Y, Brennand KJ, De Luca GC, Crary JF, Casaccia P, Buxbaum JD, Ehrlich M, Gandy S, Goate A, Katsel P, Schadt E, Haroutunian V, Zhang B (2016) Integrative network analysis of nineteen brain regions identifies molecular signatures and networks underlying selective regional vulnerability to Alzheimer's disease. Genome Med 8(1):104
Wimmer I, Tietz S, Nishihara H, Deutsch U, Sallusto F, Gosselet F, Lyck R, Muller WA, Lassmann H, Engelhardt B (2019) PECAM-1 stabilizes blood-brain barrier integrity and favors Paracellular T-cell diapedesis across the blood-brain barrier during Neuroinflammation. Front Immunol 10:711
Wurm J, Behringer SP, Ravi VM, Joseph K, Neidert N, Maier JP, Doria-Medina R, Follo M, Delev D, Pfeifer D, Beck J, Sankowski R, Schnell O, Heiland DH (2019) Astrogliosis releases pro-oncogenic chitinase 3-like 1 causing MAPK signaling in glioblastoma. Cancers 11(10):1437
Xia X, Jiang Q, McDermott J, Han JJ (2018) Aging and Alzheimer's disease: comparison and associations from molecular to system level. Aging Cell 17(5):e12802
Xiao J, Cao H, Chen J (2017) False discovery rate control incorporating phylogenetic tree increases detection power in microbiome-wide multiple testing. Bioinformatics 33(18):2873–2881
Yamamoto A, Kawahito Y (2014) The immunologic function and role of allograft inflammatory factor-1. Nihon Rinsho Men'eki Gakkai kaishi = Japanese J Clin Immunol 37(3):139–145
Yang ZF, Ho DW, Lau CK, Lam CT, Lum CT, Poon RT, Fan ST (2005) Allograft inflammatory factor-1 (AIF-1) is crucial for the survival and pro-inflammatory activity of macrophages. Int Immunol 17(11):1391–1397
Yasrebi H, Sperisen P, Praz V, Bucher P (2009) Can survival prediction be improved by merging gene expression data sets? PLoS One 4(10):e7431
Yuan HH, Chen RJ, Zhu YH, Peng CL, Zhu XR (2013) The neuroprotective effect of overexpression of calbindin-D(28k) in an animal model of Parkinson's disease. Mol Neurobiol 47(1):117–122
Zhang B, Gaiteri C, Bodea LG, Wang Z, McElwee J, Podtelezhnikov AA, Zhang C, Xie T, Tran L, Dobrin R, Fluder E, Clurman B, Melquist S, Narayanan M, Suver C, Shah H, Mahajan M, Gillis T, Mysore J, MacDonald ME, Lamb JR, Bennett DA, Molony C, Stone DJ, Gudnason V, Myers AJ, Schadt EE, Neumann H, Zhu J, Emilsson V (2013) Integrated systems approach identifies genetic nodes and networks in late-onset Alzheimer's disease. Cell 153(3):707–720
Zhou Y, Li X, Yuan X, Hao L (2019) Role of allograft inflammatory factor-1 in the regulation of inflammation and oxidative stress in primary peritoneal mesothelial cells. Cell Biol Int 43(5):495–505
Acknowledgements
We would like to show our gratitude to the authors of microarray datasets made available online, for consultation and re-analysis. In addition, we would like to express our gratitude to Mr. Asero, the technician of our laboratories, for his great willingness shown over the years and the patience that has distinguished him among our Department staff.
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Sanfilippo, C., Castrogiovanni, P., Imbesi, R. et al. CHI3L2 Expression Levels Are Correlated with AIF1, PECAM1, and CALB1 in the Brains of Alzheimer’s Disease Patients. J Mol Neurosci 70, 1598–1610 (2020). https://doi.org/10.1007/s12031-020-01667-9
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DOI: https://doi.org/10.1007/s12031-020-01667-9