Patient-derived iPSCs, a reliable in vitro model for the investigation of Alzheimer’s disease

References

Abud, E.M., Ramirez, R.N., Martinez, E.S., Healy, L.M., Nguyen, C.H.H., Newman, S.A., Yeromin, A.V., Scarfone, V.M., Marsh, S.E., Fimbres, C., . (2017). iPSC-derived human microglia-like cells to study neurological diseases. Neuron 94: 278–293, https://doi.org/10.1016/j.neuron.2017.03.042.Search in Google Scholar

Anokye-Danso, F., Snitow, M., and Morrisey, E.E. (2012). How microRNAs facilitate reprogramming to pluripotency. J. Cell Sci. 125: 4179–4187. https://doi.org/10.1242/jcs.095968.Search in Google Scholar

Area-Gomez, E., Larrea, D., Pera, M., Agrawal, R.R., Guilfoyle, D.N., Pirhaji, L., Shannon, K., Arain, H.A., Ashok, A., Chen, Q., et al.. (2020). APOE4 is associated with differential regional vulnerability to bioenergetic deficits in aged APOE mice. Sci. Rep. 10: 4277, https://doi.org/10.1038/s41598-020-61142-8.Search in Google Scholar

Balez, R., Steiner, N., Engel, M., Munoz, S.S., Lum, J.S., Wu, Y., Wang, D., Vallotton, P., Sachdev, P., O’Connor, M., et al.. (2016). Neuroprotective effects of apigenin against inflammation, neuronal excitability and apoptosis in an induced pluripotent stem cell model of Alzheimer’s disease. Sci. Rep. 6: 31450. https://doi.org/10.1038/srep31450.Search in Google Scholar

Beh-Pajooh, A. and Cantz, T. (2018). The role of microRNAs in embryonic and induced pluripotency. J. Stem Cells Regen. Med. 14: 3–9.10.46582/jsrm.1401002Search in Google Scholar

Bekris, L.M., Yu, C.E., Bird, T.D., and Tsuang, D.W. (2010). Genetics of Alzheimer disease. J. Geriatr. Psychiatr. Neurol. 23: 213–227, https://doi.org/10.1177/0891988710383571.Search in Google Scholar

Bergstrom, P., Agholme, L., Nazir, F.H., Satir, T.M., Toombs, J., Wellington, H., Strandberg, J., Bontell, T.O., Kvartsberg, H., Holmstrom, M., et al.. (2016). Amyloid precursor protein expression and processing are differentially regulated during cortical neuron differentiation. Sci. Rep. 6: 29200, https://doi.org/10.1038/srep29200.Search in Google Scholar

Birnbaum, J.H., Wanner, D., Gietl, A.F., Saake, A., Kundig, T.M., Hock, C., Nitsch, R.M., and Tackenberg, C. (2018). Oxidative stress and altered mitochondrial protein expression in the absence of amyloid-β and tau pathology in iPSC-derived neurons from sporadic Alzheimer’s disease patients. Stem Cell Res. 27: 121–130, https://doi.org/10.1016/j.scr.2018.01.019.Search in Google Scholar

Borchelt, D.R., Thinakaran, G., Eckman, C.B., Lee, M.K., Davenport, F., Ratovitsky, T., Prada, C.M., Kim, G., Seekins, S., Yager, D., et al.. (1996). Familial Alzheimer’s disease-linked presenilin 1 variants elevate Aβ1-42/1-40 ratio in vitro and in vivo. Neuron 17: 1005–1013, https://doi.org/10.1016/s0896-6273(00)80230-5.Search in Google Scholar

Brennand, K., Savas, J.N., Kim, Y., Tran, N., Simone, A., Hashimoto-Torii, K., Beaumont, K.G., Kim, H.J., Topol, A., Ladran, I., et al.. (2015). Phenotypic differences in hiPSC NPCs derived from patients with schizophrenia. Mol. Psychiatry 20: 361–368, https://doi.org/10.1038/mp.2014.22.Search in Google Scholar

Bright, J., Hussain, S., Dang, V., Wright, S., Cooper, B., Byun, T., Ramos, C., Singh, A., Parry, G., Stagliano, N., et al.. (2015). Human secreted tau increases amyloid-β production. Neurobiol. Aging 36: 693–709, https://doi.org/10.1016/j.neurobiolaging.2014.09.007.Search in Google Scholar

Cai, Z., Wan, C.Q., and Liu, Z. (2017). Astrocyte and Alzheimer’s disease. J. Neurol. Sci. 264: 2068–2074, https://doi.org/10.1007/s00415-017-8593-x.Search in Google Scholar

Cataldo, A.M., Petanceska, S., Terio, N.B., Peterhoff, C.M., Durham, R., Mercken, M., Mehta, P.D., Buxbaum, J., Haroutunian, V., and Nixon, R.A. (2004). Aβ localization in abnormal endosomes: association with earliest Abeta elevations in AD and Down syndrome. Neurobiol. Aging 25: 1263–1272, https://doi.org/10.1016/j.neurobiolaging.2004.02.027.Search in Google Scholar

Centeno, E.G.Z., Cimarosti, H., and Bithell, A. (2018). 2D versus 3D human induced pluripotent stem cell-derived cultures for neurodegenerative disease modelling. Mol. Neurodegener. 13: 27, https://doi.org/10.1186/s13024-018-0258-4.Search in Google Scholar

Chandrasekaran, A., Avci, H.X., Ochalek, A., Rosingh, L.N., Molnar, K., Laszlo, L., Bellak, T., Teglasi, A., Pesti, K., Mike, A., et al.. (2017). Comparison of 2D and 3D neural induction methods for the generation of neural progenitor cells from human induced pluripotent stem cells. Stem Cell Res. 25: 139–151, https://doi.org/10.1016/j.scr.2017.10.010.Search in Google Scholar

Chang, K.H., Lee-Chen, G.J., Huang, C.C., Lin, J.L., Chen, Y.J., Wei, P.C., Lo, Y.S., Yao, C.F., Kuo, M.W., and Chen, C.M. (2019). Modeling Alzheimer’s disease by induced pluripotent stem cells carrying APP D678H mutation. Mol. Neurobiol. 56: 3972–3983. https://doi.org/10.1007/s12035-018-1336-x.Search in Google Scholar

Chavez-Gutierrez, L., Bammens, L., Benilova, I., Vandersteen, A., Benurwar, M., Borgers, M., Lismont, S., Zhou, L., Van Cleynenbreugel, S., Esselmann, H., et al.. (2012). The mechanism of γ-secretase dysfunction in familial Alzheimer disease. EMBO J. 31: 2261–2274. https://doi.org/10.1038/emboj.2012.79.Search in Google Scholar

Chen, G.F., Xu, T.H., Yan, Y., Zhou, Y.R., Jiang, Y., Melcher, K., and Xu, H.E. (2017). Amyloid β: structure, biology and structure-based therapeutic development. Acta Pharmacol. Sin. 38: 1205–1235, https://doi.org/10.1038/aps.2017.28.Search in Google Scholar

Chen, M., Lee, H.K., Moo, L., Hanlon, E., Stein, T., and Xia, W. (2018). Common proteomic profiles of induced pluripotent stem cell-derived three-dimensional neurons and brain tissue from Alzheimer patients. J. Proteom. 182: 21–33, https://doi.org/10.1016/j.jprot.2018.04.032.Search in Google Scholar

Chighizola, M., Dini, T., Lenardi, C., Milani, P., Podesta, A., and Schulte, C. (2019). Mechanotransduction in neuronal cell development and functioning. Biophys. Rev. 11: 701–720, https://doi.org/10.1007/s12551-019-00587-2.Search in Google Scholar

Cho, H.S., Hyman, B.T., Greenberg, S.M., and Rebeck, G.W. (2001). Quantitation of apoE domains in Alzheimer disease brain suggests a role for apoE in Aβ aggregation. J. Neuropathol. Exp. Neurol. 60: 342–349, https://doi.org/10.1093/jnen/60.4.342.Search in Google Scholar

Choi, H., Kim, H.J., Yang, J., Chae, S., Lee, W., Chung, S., Kim, J., Song, H., Lee, C.K., Jun, J.H., et al.. (2020). Acetylation changes tau interactome to degrade tau in Alzheimer’s disease animal and organoid models. Aging Cell 19: e13081, https://doi.org/10.1111/acel.13081.Search in Google Scholar

Chung, W.S., Verghese, P.B., Chakraborty, C., Joung, J., Hyman, B.T., Ulrich, J.D., Holtzman, D.M., and Barres, B.A. (2016). Novel allele-dependent role for APOE in controlling the rate of synapse pruning by astrocytes. Proc. Natl. Acad. Sci. U.S.A. 113: 10186–10191, https://doi.org/10.1073/pnas.1609896113.Search in Google Scholar

Cobb, L.J., Lee, C., Xiao, J., Yen, K., Wong, R.G., Nakamura, H.K., Mehta, H.H., Gao, Q., Ashur, C., Huffman, D.M., et al.. (2016). Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers. Aging (Albany NY) 8: 796–809, https://doi.org/10.18632/aging.100943.Search in Google Scholar

Crossgrove, J.S., Li, G.J., and Zheng, W. (2005). The choroid plexus removes β-amyloid from brain cerebrospinal fluid. Exp. Biol. Med. (Maywood) 230: 771–776, https://doi.org/10.1177/153537020523001011.Search in Google Scholar

Cummings, J., Lee, G., Ritter, A., Sabbagh, M., and Zhong, K. (2019). Alzheimer’s disease drug development pipeline, 2019. Alzheimers Dement 5: 272–293, https://doi.org/10.1016/j.trci.2019.05.008.Search in Google Scholar

D’Avanzo, C., Aronson, J., Kim, Y.H., Choi, S.H., Tanzi, R.E., and Kim, D.Y. (2015). Alzheimer’s in 3D culture: challenges and perspectives. Bioessays 37: 1139–1148, https://doi.org/10.1002/bies.201500063.Search in Google Scholar

De Strooper, B. (2007). Loss-of-function presenilin mutations in Alzheimer disease. Talking Point on the role of presenilin mutations in Alzheimer disease. EMBO Rep. 8: 141–146, https://doi.org/10.1038/sj.embor.7400897.Search in Google Scholar

Doss, M.X. and Sachinidis, A. (2019). Current challenges of iPSC-based disease modeling and therapeutic implications. Cells 8: 403, https://doi.org/10.3390/cells8050403.Search in Google Scholar

Douvaras, P. and Fossati, V. (2015). Generation and isolation of oligodendrocyte progenitor cells from human pluripotent stem cells. Nat. Protoc. 10: 1143–1154, https://doi.org/10.1038/nprot.2015.075.Search in Google Scholar

Douvaras, P., Sun, B., Wang, M., Kruglikov, I., Lallos, G., Zimmer, M., Terrenoire, C., Zhang, B., Gandy, S., Schadt, E., et al.. (2017). Directed differentiation of human pluripotent stem cells to microglia. Stem Cell Reports 8: 1516–1524, https://doi.org/10.1016/j.stemcr.2017.04.023.Search in Google Scholar

Duan, L., Bhattacharyya, B.J., Belmadani, A., Pan, L., Miller, R.J., and Kessler, J.A. (2014). Stem cell derived basal forebrain cholinergic neurons from Alzheimer’s disease patients are more susceptible to cell death. Mol. Neurodegener. 9: 3, https://doi.org/10.1186/1750-1326-9-3.Search in Google Scholar

Edmondson, R., Broglie, J.J., Adcock, A.F., and Yang, L. (2014). Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors. Assay Drug Dev. Technol. 12: 207–218, https://doi.org/10.1089/adt.2014.573.Search in Google Scholar

Egan, M.F., Kost, J., Tariot, P.N., Aisen, P.S., Cummings, J.L., Vellas, B., Sur, C., Mukai, Y., Voss, T., Furtek, C., et al.. (2018). Randomized trial of Verubecestat for mild-to-moderate Alzheimer’s disease. N. Engl. J. Med. 378: 1691–1703, https://doi.org/10.1056/nejmoa1706441.Search in Google Scholar

Ehrlich, M., Mozafari, S., Glatza, M., Starost, L., Velychko, S., Hallmann, A.L., Cui, Q.L., Schambach, A., Kim, K.P., Bachelin, C., et al.. (2017). Rapid and efficient generation of oligodendrocytes from human induced pluripotent stem cells using transcription factors. Proc. Natl. Acad. Sci. U.S.A. 114: E2243–E2252, https://doi.org/10.1073/pnas.1614412114.Search in Google Scholar

Feldman, H.H., Doody, R.S., Kivipelto, M., Sparks, D.L., Waters, D.D., Jones, R.W., Schwam, E., Schindler, R., Hey-Hadavi, J., DeMicco, D.A., et al.. (2010). Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe. Neurology 74: 956–964, https://doi.org/10.1212/wnl.0b013e3181d6476a.Search in Google Scholar

Flamier, A., El Hajjar, J., Adjaye, J., Fernandes, K.J., Abdouh, M., and Bernier, G. (2018). Modeling late-onset sporadic Alzheimer’s disease through BMI1 deficiency. Cell Rep. 23: 2653–2666,https://doi.org/10.1016/j.celrep.2018.04.097.Search in Google Scholar

Frega, M., Tedesco, M., Massobrio, P., Pesce, M., and Martinoia, S. (2014). Network dynamics of 3D engineered neuronal cultures: a new experimental model for in-vitro electrophysiology. Sci. Rep. 4: 5489, https://doi.org/10.1038/srep05489.Search in Google Scholar

Gaspar-Maia, A., Alajem, A., Meshorer, E., and Ramalho-Santos, M. (2011). Open chromatin in pluripotency and reprogramming. Nat. Rev. Mol. Cell Biol. 12: 36–47, https://doi.org/10.1038/nrm3036.Search in Google Scholar

Ghatak, S., Dolatabadi, N., Gao, R., Wu, Y., Scott, H., Trudler, D., Sultan, A., Ambasudhan, R., Nakamura, T., Masliah, E., et al.. (2020). NitroSynapsin ameliorates hypersynchronous neural network activity in Alzheimer hiPSC models. Mol. Psychiatry, https://doi.org/10.1038/s41380-020-0776-7.Search in Google Scholar

Ghatak, S., Dolatabadi, N., Trudler, D., Zhang, X., Wu, Y., Mohata, M., Ambasudhan, R., Talantova, M., and Lipton, S.A. (2019). Mechanisms of hyperexcitability in Alzheimer’s disease hiPSC-derived neurons and cerebral organoids vs isogenic controls. eLife 8: e50333. https://doi.org/10.7554/elife.50333.Search in Google Scholar

Ginhoux, F., Greter, M., Leboeuf, M., Nandi, S., See, P., Gokhan, S., Mehler, M.F., Conway, S.J., Ng, L.G., Stanley, E.R., et al.. (2010). Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330: 841–845, https://doi.org/10.1126/science.1194637.Search in Google Scholar

Goate, A.M. (1998). Monogenetic determinants of Alzheimer’s disease: APP mutations. Cell. Mol. Life Sci. 54: 897–901, https://doi.org/10.1007/s000180050218.Search in Google Scholar

Gonzalez, C., Armijo, E., Bravo-Alegria, J., Becerra-Calixto, A., Mays, C.E., and Soto, C. (2018). Modeling amyloid beta and tau pathology in human cerebral organoids. Mol. Psychiatry 23: 2363–2374, https://doi.org/10.1038/s41380-018-0229-8.Search in Google Scholar

Gonzalez-Marrero, I., Gimenez-Llort, L., Johanson, C.E., Carmona-Calero, E.M., Castaneyra-Ruiz, L., Brito-Armas, J.M., Castaneyra-Perdomo, A., and Castro-Fuentes, R. (2015). Choroid plexus dysfunction impairs beta-amyloid clearance in a triple transgenic mouse model of Alzheimer’s disease. Front. Cell. Neurosci. 9: 17. https://doi.org/10.3389/fncel.2015.00017.Search in Google Scholar

Hall, A.R., Burke, N., Dongworth, R.K., and Hausenloy, D.J. (2014). Mitochondrial fusion and fission proteins: novel therapeutic targets for combating cardiovascular disease. Br. J. Pharmacol. 171: 1890–1906, https://doi.org/10.1111/bph.12516.Search in Google Scholar

Hansson, O., Lehmann, S., Otto, M., Zetterberg, H., and Lewczuk, P. (2019). Advantages and disadvantages of the use of the CSF Amyloid beta (Aβ) 42/40 ratio in the diagnosis of Alzheimer’s Disease. Alzheimer’s Res. Ther. 11: 34, https://doi.org/10.1186/s13195-019-0485-0.Search in Google Scholar

Hansson, O., Zetterberg, H., Buchhave, P., Andreasson, U., Londos, E., Minthon, L., and Blennow, K. (2007). Prediction of Alzheimer’s disease using the CSF Aβ42/Aβ40 ratio in patients with mild cognitive impairment. Dement. Geriatr. Cognit. Disord. 23: 316–320, https://doi.org/10.1159/000100926.Search in Google Scholar

Harris, F.M., Brecht, W.J., Xu, Q., Tesseur, I., Kekonius, L., Wyss-Coray, T., Fish, J.D., Masliah, E., Hopkins, P.C., Scearce-Levie, K., . (2003). Carboxyl-terminal-truncated apolipoprotein E4 causes Alzheimer’s disease-like neurodegeneration and behavioral deficits in transgenic mice. PNAS 100: 10966–10971, https://doi.org/10.1073/pnas.1434398100.Search in Google Scholar

Heinisch, J.J. and Brandt, R. (2016). Signaling pathways and posttranslational modifications of tau in Alzheimer’s disease: the humanization of yeast cells. Microbial Cell 3: 135–146, https://doi.org/10.15698/mic2016.04.489.Search in Google Scholar

Henley, D., Raghavan, N., Sperling, R., Aisen, P., Raman, R., and Romano, G. (2019). Preliminary results of a trial of Atabecestat in preclinical Alzheimer’s disease. N. Engl. J. Med. 380: 1483–1485, https://doi.org/10.1056/nejmc1813435.Search in Google Scholar

Hernandez-Sapiens, M.A., Reza-Zaldivar, E.E., Cevallos, R.R., Marquez-Aguirre, A.L., Gazarian, K., and Canales-Aguirre, A.A. (2020). A three-dimensional Alzheimer’s disease cell culture model using iPSC-derived neurons carrying A246E mutation in PSEN1. Front. Cell. Neurosci. 14: 151, https://doi.org/10.3389/fncel.2020.00151.Search in Google Scholar

Hoffmann, A., Ziller, M., and Spengler, D. (2019). Progress in iPSC-based modeling of Psychiatric disorders. Int. J. Mol. Sci. 20: 4896, https://doi.org/10.3390/ijms20194896.Search in Google Scholar

Holmes, B.B., Furman, J.L., Mahan, T.E., Yamasaki, T.R., Mirbaha, H., Eades, W.C., Belaygorod, L., Cairns, N.J., Holtzman, D.M., and Diamond, M.I. (2014). Proteopathic tau seeding predicts tauopathy in vivo. Proc. Natl. Acad. Sci. U.S.A. 111: E4376–E4385. https://doi.org/10.1073/pnas.1411649111.Search in Google Scholar

Hossini, A.M., Megges, M., Prigione, A., Lichtner, B., Toliat, M.R., Wruck, W., Schroter, F., Nuernberg, P., Kroll, H., Makrantonaki, E., et al.. (2015). Induced pluripotent stem cell-derived neuronal cells from a sporadic Alzheimer’s disease donor as a model for investigating AD-associated gene regulatory networks. BMC Genom. 16: 84, https://doi.org/10.1186/s12864-015-1262-5.Search in Google Scholar

Hu, N.W., Corbett, G.T., Moore, S., Klyubin, I., O’Malley, T.T., Walsh, D.M., Livesey, F.J., and Rowan, M.J. (2018). Extracellular forms of Aβ and tau from iPSC models of Alzheimer’s disease disrupt synaptic plasticity. Cell Rep. 23: 1932–1938, https://doi.org/10.1016/j.celrep.2018.04.040.Search in Google Scholar

Huang, Y., Liu, X.Q., Wyss-Coray, T., Brecht, W.J., Sanan, D.A., and Mahley, R.W. (2001). Apolipoprotein E fragments present in Alzheimer’s disease brains induce neurofibrillary tangle-like intracellular inclusions in neurons. Proc. Natl. Acad. Sci. U. S. A. 98: 8838–8843, https://doi.org/10.1073/pnas.151254698.Search in Google Scholar

Israel, M.A., Yuan, S.H., Bardy, C., Reyna, S.M., Mu, Y., Herrera, C., Hefferan, M.P., Van Gorp, S., Nazor, K.L., Boscolo, F.S., Carson, C.T., Laurent, L.C., Marsala, M., Gage, F.H., Remes, A.M., Koo, E.H., and Goldstein, L.S. (2012). Probing sporadic and familial Alzheimer’s disease using induced pluripotent stem cells. Nature 482: 216–220, https://doi.org/10.1038/nature10821.Search in Google Scholar

Janelidze, S., Zetterberg, H., Mattsson, N., Palmqvist, S., Vanderstichele, H., Lindberg, O., van Westen, D., Stomrud, E., Minthon, L., Blennow, K., et al.. (2016). CSF Aβ42/Aβ40 and Aβ42/Aβ38 ratios: better diagnostic markers of Alzheimer disease. Ann. Clin. Transl. Neurol. 3: 154–165, https://doi.org/10.1002/acn3.274.Search in Google Scholar

Jones, V.C., Atkinson-Dell, R., Verkhratsky, A., and Mohamet, L. (2017). Aberrant iPSC-derived human astrocytes in Alzheimer’s disease. Cell Death Dis. 8: e2696, https://doi.org/10.1038/cddis.2017.89.Search in Google Scholar

Jorfi, M., D’Avanzo, C., Tanzi, R.E., Kim, D.Y., and Irimia, D. (2018). Human neurospheroid arrays for in vitro studies of Alzheimer’s disease. Sci. Rep. 8: 2450, https://doi.org/10.1038/s41598-018-20436-8.Search in Google Scholar

Joung, J.K. and Sander, J.D. (2012). TALENs: a widely applicable technology for targeted genome editing. Nat. Rev. Mol. Cell Biol. 14: 49–55, https://doi.org/10.1038/nrm3486.Search in Google Scholar

Kapalczynska, M., Kolenda, T., Przybyla, W., Zajaczkowska, M., Teresiak, A., Filas, V., Ibbs, M., Blizniak, R., Luczewski, L., and Lamperska, K. (2018). 2D and 3D cell cultures - a comparison of different types of cancer cell cultures. Arch. Med. Sci. 14: 910–919.Search in Google Scholar

Karimi, M., Bahrami, S., Mirshekari, H., Basri, S.M., Nik, A.B., Aref, A.R., Akbari, M., and Hamblin, M.R. (2016). Microfluidic systems for stem cell-based neural tissue engineering. Lab Chip 16: 2551–2571, https://doi.org/10.1039/c6lc00489j.Search in Google Scholar

Keene, C.D., Darvas, M., Kraemer, B., Liggitt, D., Sigurdson, C., and Ladiges, W. (2016). Neuropathological assessment and validation of mouse models for Alzheimer’s disease: applying NIA-AA guidelines. Pathobiol. Aging Age Relat. Dis. 6: 32397, https://doi.org/10.3402/pba.v6.32397.Search in Google Scholar

Kierdorf, K., Erny, D., Goldmann, T., Sander, V., Schulz, C., Perdiguero, E.G., Wieghofer, P., Heinrich, A., Riemke, P., Holscher, C., et al.. (2013). Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways. Nat. Neurosci. 16: 273–280, https://doi.org/10.1038/nn.3318.Search in Google Scholar

Kim, Y.H., Choi, S.H., D’Avanzo, C., Hebisch, M., Sliwinski, C., Bylykbashi, E., Washicosky, K.J., Klee, J.B., Brustle, O., Tanzi, R.E., et al.. (2015). A 3D human neural cell culture system for modeling Alzheimer’s disease. Nat. Protoc. 10: 985–1006, https://doi.org/10.1038/nprot.2015.065.Search in Google Scholar

Kim, M., Suh, J., Romano, D., Truong, M.H., Mullin, K., Hooli, B., Norton, D., Tesco, G., Elliott, K., Wagner, S.L., et al.. (2009). Potential late-onset Alzheimer’s disease-associated mutations in the ADAM10 gene attenuate α-secretase activity. Hum. Mol. Genet. 18: 3987–3996, https://doi.org/10.1093/hmg/ddp323.Search in Google Scholar

Kitazawa, M., Cheng, D., Tsukamoto, M.R., Koike, M.A., Wes, P.D., Vasilevko, V., Cribbs, D.H., and LaFerla, F.M. (2011). Blocking IL-1 signaling rescues cognition, attenuates tau pathology, and restores neuronal beta-catenin pathway function in an Alzheimer’s disease model. J. Immunol. 187: 6539–6549, https://doi.org/10.4049/jimmunol.1100620.Search in Google Scholar

Kondo, T., Asai, M., Tsukita, K., Kutoku, Y., Ohsawa, Y., Sunada, Y., Imamura, K., Egawa, N., Yahata, N., Okita, K., et al.. (2013). Modeling Alzheimer’s disease with iPSCs reveals stress phenotypes associated with intracellular Aβand differential drug responsiveness. Cell Stem Cell 12: 487–496, https://doi.org/10.1016/j.stem.2013.01.009.Search in Google Scholar

Konttinen, H., Cabral-da-Silva, M.E.C., Ohtonen, S., Wojciechowski, S., Shakirzyanova, A., Caligola, S., Giugno, R., Ishchenko, Y., Hernandez, D., Fazaludeen, M.F., et al.. (2019). PSEN1DeltaE9, APPswe, and APOE4 confer disparate phenotypes in human iPSC-derived microglia. Stem Cell Rep. 13: 669–683, https://doi.org/10.1016/j.stemcr.2019.08.004.Search in Google Scholar

Krishnakumar, R., and Blelloch, R.H. (2013). Epigenetics of cellular reprogramming. Curr. Opin. Genet. Dev. 23: 548–555, https://doi.org/10.1016/j.gde.2013.06.005.Search in Google Scholar

Kumar, A., Singh, A., and Ekavali (2015). A review on Alzheimer’s disease pathophysiology and its management: an update. Pharmacol. Rep. 67: 195–203, https://doi.org/10.1016/j.pharep.2014.09.004.Search in Google Scholar

Lanoiselee, H.M., Nicolas, G., Wallon, D., Rovelet-Lecrux, A., Lacour, M., Rousseau, S., Richard, A.C., Pasquier, F., Rollin-Sillaire, A., Martinaud, O., et al.. (2017). APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: a genetic screening study of familial and sporadic cases. PLoS Med. 14: e1002270, https://doi.org/10.1371/journal.pmed.1002270.Search in Google Scholar

Lee, J.C., Kim, S.J., Hong, S., and Kim, Y. (2019). Diagnosis of Alzheimer’s disease utilizing amyloid and tau as fluid biomarkers. Exp. Mol. Med. 51: 1–10, https://doi.org/10.1038/s12276-019-0250-2.Search in Google Scholar

Lee, H.K., Velazquez Sanchez, C., Chen, M., Morin, P.J., Wells, J.M., Hanlon, E.B., and Xia, W. (2016). Three dimensional human neuro-spheroid model of Alzheimer’s disease based on differentiated induced pluripotent stem cells. PloS One 11: e0163072, https://doi.org/10.1371/journal.pone.0163072.Search in Google Scholar

Lewczuk, P., Esselmann, H., Meyer, M., Wollscheid, V., Neumann, M., Otto, M., Maler, J.M., Ruther, E., Kornhuber, J., and Wiltfang, J. (2003). The amyloid-beta (Abeta) peptide pattern in cerebrospinal fluid in Alzheimer’s disease: evidence of a novel carboxyterminally elongated Aβ peptide. Rapid Commun. Mass Spectrom. 17: 1291–1296, https://doi.org/10.1002/rcm.1048.Search in Google Scholar

Li, X., Bao, X., and Wang, R. (2016). Experimental models of Alzheimer’s disease for deciphering the pathogenesis and therapeutic screening (review). Int. J. Mol. Med. 37: 271–283, https://doi.org/10.3892/ijmm.2015.2428.Search in Google Scholar

Li, L., Kim, H.J., Roh, J.H., Kim, M., Koh, W., Kim, Y., Heo, H., Chung, J., Nakanishi, M., Yoon, T., et al.. (2020). Pathological manifestation of the induced pluripotent stem cell-derived cortical neurons from an early-onset Alzheimer’s disease patient carrying a presenilin-1 mutation (S170F). Cell Prolif. 53: e12798, https://doi.org/10.1111/cpr.12798.Search in Google Scholar

Li, L., Roh, J.H., Chang, E.H., Lee, Y., Lee, S., Kim, M., Koh, W., Chang, J.W., Kim, H.J., Nakanishi, M., et al.. (2018a). iPSC modeling of Presenilin1 mutation in Alzheimer’s disease with cerebellar Ataxia. Exp. Neurobiol. 27: 350–364, https://doi.org/10.5607/en.2018.27.5.350.Search in Google Scholar

Li, L., Roh, J.H., Kim, H.J., Park, H.J., Kim, M., Koh, W., Heo, H., Chang, J.W., Nakanishi, M., Yoon, T., et al.. (2019). The first generation of iPSC line from a Korean Alzheimer’s disease patient carrying APP-V715M mutation exhibits a distinct mitochondrial dysfunction. Exp. Neurobiol. 28: 329–336, https://doi.org/10.5607/en.2019.28.3.329.Search in Google Scholar

Li, X., Tao, Y., Bradley, R., Du, Z., Kong, L., Dong, Y., Jones, J., Yan, Y., Harder, C.R.K., Friedman, L.M., et al.. (2018b). Fast generation of functional subtype Astrocytes from human pluripotent stem cells. Stem Cell Rep. 11: 998–1008, https://doi.org/10.1016/j.stemcr.2018.08.019.Search in Google Scholar

Lin, Y.T., Seo, J., Gao, F., Feldman, H.M., Wen, H.L., Penney, J., Cam, H.P., Gjoneska, E., Raja, W.K., Cheng, J., Rueda, R., Kritskiy, O., Abdurrob, F., Peng, Z., Milo, B., Yu, C.J., Elmsaouri, S., Dey, D., Ko, T., Yankner, B.A., and Tsai, L.H. (2018). APOE4 causes widespread molecular and cellular alterations associated with Alzheimer’s disease phenotypes in human iPSC-derived brain cell types. Neuron 98: 1141 e1147–1154 e1147, https://doi.org/10.1016/j.neuron.2018.05.008.Search in Google Scholar

Liu, P.P., Xie, Y., Meng, X.Y., and Kang, J.S. (2019). History and progress of hypotheses and clinical trials for Alzheimer’s disease. Signal Transduct. Target Ther. 4: 29, https://doi.org/10.1038/s41392-019-0071-8.Search in Google Scholar

Ma, J., Guo, R., Song, Y., Zhang, J., Feng, B., Amponsah, A.E., Kong, D., He, J., Zhang, W., Liu, A., et al.. (2019). Generation and characterization of a human induced pluripotent stem cell (iPSC) line (HEBHMUi001-A) from a sporadic Parkinson’s disease patient. Stem Cell Res. 36: 101417, https://doi.org/10.1016/j.scr.2019.101417.Search in Google Scholar

Masters, C.L., Bateman, R., Blennow, K., Rowe, C.C., Sperling, R.A., and Cummings, J.L. (2015). Alzheimer’s disease. Nat. Rev. Dis. Primers 1: 15056, https://doi.org/10.1038/nrdp.2015.56.Search in Google Scholar

McQuade, A., Coburn, M., Tu, C.H., Hasselmann, J., Davtyan, H., and Blurton-Jones, M. (2018). Development and validation of a simplified method to generate human microglia from pluripotent stem cells. Mol. Neurodegener. 13: 67, https://doi.org/10.1186/s13024-018-0297-x.Search in Google Scholar

Mehta, P.D., Pirttila, T., Mehta, S.P., Sersen, E.A., Aisen, P.S., and Wisniewski, H.M. (2000). Plasma and cerebrospinal fluid levels of amyloid β proteins 1-40 and 1-42 in Alzheimer disease. Arch. Neurol. 57: 100–105, https://doi.org/10.1001/archneur.57.1.100.Search in Google Scholar

Mertens, J., Stuber, K., Wunderlich, P., Ladewig, J., Kesavan, J.C., Vandenberghe, R., Vandenbulcke, M., van Damme, P., Walter, J., Brustle, O., et al.. (2013). APP processing in human pluripotent stem cell-derived neurons is resistant to NSAID-based gamma-secretase modulation. Stem Cell Rep. 1: 491–498, https://doi.org/10.1016/j.stemcr.2013.10.011.Search in Google Scholar

Meyer, K., Feldman, H.M., Lu, T., Drake, D., Lim, E.T., Ling, K.H., Bishop, N.A., Pan, Y., Seo, J., Lin, Y.T., Su, S.C., Church, G.M., Tsai, L.H., and Yankner, B.A. (2019). REST and neural gene network dysregulation in iPSC models of Alzheimer’s disease. Cell Rep. 26: 1112–1127, https://doi.org/10.1016/j.celrep.2019.01.023.Search in Google Scholar

Mollinari, C., Zhao, J., Lupacchini, L., Garaci, E., Merlo, D., and Pei, G. (2018). Transdifferentiation: a new promise for neurodegenerative diseases. Cell Death Dis. 9: 830, https://doi.org/10.1038/s41419-018-0891-4.Search in Google Scholar

Moore, S., Evans, L.D., Andersson, T., Portelius, E., Smith, J., Dias, T.B., Saurat, N., McGlade, A., Kirwan, P., Blennow, K., et al.. (2015). APP metabolism regulates tau proteostasis in human cerebral cortex neurons. Cell Rep. 11: 689–696, https://doi.org/10.1016/j.celrep.2015.03.068.Search in Google Scholar

Moreno, C.L., Della Guardia, L., Shnyder, V., Ortiz-Virumbrales, M., Kruglikov, I., Zhang, B., Schadt, E.E., Tanzi, R.E., Noggle, S., Buettner, C., et al.. (2018). iPSC-derived familial Alzheimer’s PSEN2 (N141I) cholinergic neurons exhibit mutation-dependent molecular pathology corrected by insulin signaling. Mol. Neurodegener. 13: 33, https://doi.org/10.1186/s13024-018-0265-5.Search in Google Scholar

Mouchard, A., Boutonnet, M.C., Mazzocco, C., Biendon, N., and Macrez, N. (2019). ApoE-fragment/Aβ heteromers in the brain of patients with Alzheimer’s disease. Sci. Rep. 9: 3989, https://doi.org/10.1038/s41598-019-40438-4.Search in Google Scholar

Muratore, C.R., Rice, H.C., Srikanth, P., Callahan, D.G., Shin, T., Benjamin, L.N., Walsh, D.M., Selkoe, D.J., and Young-Pearse, T.L. (2014). The familial Alzheimer’s disease APPV717I mutation alters APP processing and Tau expression in iPSC-derived neurons. Hum. Mol. Genet. 23: 3523–3536, https://doi.org/10.1093/hmg/ddu064.Search in Google Scholar

Muth, C., Hartmann, A., Sepulveda-Falla, D., Glatzel, M., and Krasemann, S. (2019). Phagocytosis of apoptotic cells is specifically upregulated in ApoE4 expressing microglia in vitro. Front. Cell. Neurosci. 13: 181, https://doi.org/10.3389/fncel.2019.00181.Search in Google Scholar

Nehme, R., Zuccaro, E., Ghosh, S.D., Li, C., Sherwood, J.L., Pietilainen, O., Barrett, L.E., Limone, F., Worringer, K.A., Kommineni, S., et al.. (2018). Combining NGN2 programming with developmental patterning generates human excitatory neurons with NMDAR-mediated synaptic transmission. Cell Rep. 23: 2509–2523, https://doi.org/10.1016/j.celrep.2018.04.066.Search in Google Scholar

Nelson, T.J. and Sen, A. (2019). Apolipoprotein E particle size is increased in Alzheimer’s disease. Alzheimers Dement. (Amst) 11: 10–18, https://doi.org/10.1016/j.dadm.2018.10.005.Search in Google Scholar

Nethercott, H.E., Brick, D.J., and Schwartz, P.H. (2011). Derivation of induced pluripotent stem cells by lentiviral transduction. Methods Mol. Biol. 767: 67–85, https://doi.org/10.1007/978-1-61779-201-4_6.Search in Google Scholar

Nilsberth, C., Westlind-Danielsson, A., Eckman, C.B., Condron, M.M., Axelman, K., Forsell, C., Stenh, C., Luthman, J., Teplow, D.B., Younkin, S.G., et al.. (2001). The ’Arctic’ APP mutation (E693G) causes Alzheimer’s disease by enhanced Aβ protofibril formation. Nat. Neurosci. 4: 887–893, https://doi.org/10.1038/nn0901-887.Search in Google Scholar

Niwa, H (2014). The pluripotency transcription factor network at work in reprogramming. Curr. Opin. Genet. Dev. 28: 25–31, https://doi.org/10.1016/j.gde.2014.08.004.Search in Google Scholar

Nixon, R.A. (2005). Endosome function and dysfunction in Alzheimer’s disease and other neurodegenerative diseases. Neurobiol. Aging 26: 373–382, https://doi.org/10.1016/j.neurobiolaging.2004.09.018.Search in Google Scholar

Nuriel, T., Angulo, S.L., Khan, U., Ashok, A., Chen, Q., Figueroa, H.Y., Emrani, S., Liu, L., Herman, M., Barrett, G., et al.. (2017). Neuronal hyperactivity due to loss of inhibitory tone in APOE4 mice lacking Alzheimer’s disease-like pathology. Nat. Commun. 8: 1464, https://doi.org/10.1038/s41467-017-01444-0.Search in Google Scholar

Ochalek, A., Mihalik, B., Avci, H.X., Chandrasekaran, A., Teglasi, A., Bock, I., Giudice, M.L., Tancos, Z., Molnar, K., Laszlo, L., et al.. (2017). Neurons derived from sporadic Alzheimer’s disease iPSCs reveal elevated TAU hyperphosphorylation, increased amyloid levels, and GSK3B activation. Alzheimer’s Res. Ther. 9: 90, https://doi.org/10.1186/s13195-017-0317-z.Search in Google Scholar

Oikari, L.E., Pandit, R., Stewart, R., Cuni-Lopez, C., Quek, H., Sutharsan, R., Rantanen, L.M., Oksanen, M., Lehtonen, S., de Boer, C.M., et al.. (2020). Altered brain endothelial cell phenotype from a familial Alzheimer mutation and its potential implications for amyloid clearance and drug delivery. Stem Cell Rep. 14: 924–939, https://doi.org/10.1016/j.stemcr.2020.03.011.Search in Google Scholar

Oksanen, M., Petersen, A.J., Naumenko, N., Puttonen, K., Lehtonen, S., Gubert Olive, M., Shakirzyanova, A., Leskela, S., Sarajarvi, T., Viitanen, M., et al.. (2017). PSEN1 mutant iPSC-derived model reveals severe astrocyte pathology in Alzheimer’s disease. Stem Cell Rep. 9: 1885–1897, https://doi.org/10.1016/j.stemcr.2017.10.016.Search in Google Scholar

Omole, A.E. and Fakoya, A.O.J. (2018). Ten years of progress and promise of induced pluripotent stem cells: historical origins, characteristics, mechanisms, limitations, and potential applications. Peer J. 6: e4370, https://doi.org/10.7717/peerj.4370.Search in Google Scholar

Osaki, T., Sivathanu, V., and Kamm, R.D. (2018). Engineered 3D vascular and neuronal networks in a microfluidic platform. Sci. Rep. 8: 5168, https://doi.org/10.1038/s41598-018-23512-1.Search in Google Scholar

Papadimitriou, C., Celikkaya, H., Cosacak, M.I., Mashkaryan, V., Bray, L., Bhattarai, P., Brandt, K., Hollak, H., Chen, X., He, S., et al.. (2018). 3D culture method for Alzheimer’s disease modeling reveals interleukin-4 rescues Aβ42-induced loss of human neural stem cell plasticity. Dev. Cell 46: 85–101, https://doi.org/10.1016/j.devcel.2018.06.005.Search in Google Scholar

Parcon, P.A., Balasubramaniam, M., Ayyadevara, S., Jones, R.A., Liu, L., Shmookler Reis, R.J., Barger, S.W., Mrak, R.E., and Griffin, W.S.T. (2018). Apolipoprotein E4 inhibits autophagy gene products through direct, specific binding to CLEAR motifs. Alzheimers. Dement. 14: 230–242, https://doi.org/10.1016/j.jalz.2017.07.754.Search in Google Scholar

Park, J., Lee, B.K., Jeong, G.S., Hyun, J.K., Lee, C.J., and Lee, S.H. (2015). Three-dimensional brain-on-a-chip with an interstitial level of flow and its application as an in vitro model of Alzheimer’s disease. Lab Chip 15: 141–150, https://doi.org/10.1039/c4lc00962b.Search in Google Scholar

Park, J., Wetzel, I., Marriott, I., Dreau, D., D’Avanzo, C., Kim, D.Y., Tanzi, R.E., and Cho, H. (2018). A 3D human triculture system modeling neurodegeneration and neuroinflammation in Alzheimer’s disease. Nat. Neurosci. 21: 941–951, https://doi.org/10.1038/s41593-018-0175-4.Search in Google Scholar

Pavoni, S., Jarray, R., Nassor, F., Guyot, A.C., Cottin, S., Rontard, J., Mikol, J., Mabondzo, A., Deslys, J.P., and Yates, F. (2018). Small-molecule induction of Aβ-42 peptide production in human cerebral organoids to model Alzheimer’s disease associated phenotypes. PloS One 13: e0209150, https://doi.org/10.1371/journal.pone.0209150.Search in Google Scholar

Pontes Soares, C., Midlej, V., de Oliveira, M.E., Benchimol, M., Costa, M.L., and Mermelstein, C. (2012). 2D and 3D-organized cardiac cells shows differences in cellular morphology, adhesion junctions, presence of myofibrils and protein expression. PloS One 7: e38147, https://doi.org/10.1371/journal.pone.0038147.Search in Google Scholar

Portelius, E., Andreasson, U., Ringman, J.M., Buerger, K., Daborg, J., Buchhave, P., Hansson, O., Harmsen, A., Gustavsson, M.K., Hanse, E., et al.. (2010). Distinct cerebrospinal fluid amyloid β peptide signatures in sporadic and PSEN1 A431E-associated familial Alzheimer’s disease. Mol. Neurodegener. 5: 2, https://doi.org/10.1186/1750-1326-5-2.Search in Google Scholar

Prvulovic, D. and Hampel, H. (2011). Amyloid beta (Aβ) and phospho-tau (p-tau) as diagnostic biomarkers in Alzheimer’s disease. Clin. Chem. Lab. Med. 49: 367–374, https://doi.org/10.1515/cclm.2011.087.Search in Google Scholar

Qin, H., Zhao, A., Zhang, C., and Fu, X. (2016). Epigenetic control of reprogramming and transdifferentiation by histone modifications. Stem Cell Rev. Rep. 12: 708–720, https://doi.org/10.1007/s12015-016-9682-4.Search in Google Scholar

Quinn, J.F., Raman, R., Thomas, R.G., Yurko-Mauro, K., Nelson, E.B., Van Dyck, C., Galvin, J.E., Emond, J., Jack, C.R.Jr., Weiner, M., et al.. (2010). Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. J. Am. Med. Assoc. 304: 1903–1911, https://doi.org/10.1001/jama.2010.1510.Search in Google Scholar

Raja, W.K., Mungenast, A.E., Lin, Y.T., Ko, T., Abdurrob, F., Seo, J., and Tsai, L.H. (2016). Self-organizing 3D human neural tissue derived from induced pluripotent stem cells recapitulate Alzheimer’s disease phenotypes. PLoS One 11: e0161969, https://doi.org/10.1371/journal.pone.0161969.Search in Google Scholar

Rasmussen, M.A., Holst, B., Tumer, Z., Johnsen, M.G., Zhou, S., Stummann, T.C., Hyttel, P., and Clausen, C. (2014). Transient p53 suppression increases reprogramming of human fibroblasts without affecting apoptosis and DNA damage. Stem Cell Rep 3: 404–413, https://doi.org/10.1016/j.stemcr.2014.07.006.Search in Google Scholar

Ries, M. and Sastre, M. (2016). Mechanisms of Aβ clearance and degradation by glial cells. Front. Aging Neurosci. 8: 160, https://doi.org/10.3389/fnagi.2016.00160.Search in Google Scholar

Rosen, C., Andreasson, U., Mattsson, N., Marcusson, J., Minthon, L., Andreasen, N., Blennow, K., and Zetterberg, H. (2012). Cerebrospinal fluid profiles of amyloid β-related biomarkers in Alzheimer’s disease. Neuromol. Med. 14: 65–73, https://doi.org/10.1007/s12017-012-8171-4.Search in Google Scholar

Rowland, H.A., Hooper, N.M., and Kellett, K.A.B. (2018). Modelling sporadic Alzheimer’s disease using induced pluripotent stem cells. Neurochem. Res. 43: 2179–2198, https://doi.org/10.1007/s11064-018-2663-z.Search in Google Scholar

Sarkar, A., Mei, A., Paquola, A.C.M., Stern, S., Bardy, C., Klug, J.R., Kim, S., Neshat, N., Kim, H.J., Ku, M., et al.. (2018). Efficient generation of CA3 neurons from human pluripotent stem cells enables modeling of hippocampal connectivity in vitro. Cell Stem Cell 22: 684–697, https://doi.org/10.1016/j.stem.2018.04.009.Search in Google Scholar

Scheuner, D., Eckman, C., Jensen, M., Song, X., Citron, M., Suzuki, N., Bird, T.D., Hardy, J., Hutton, M., Kukull, W., et al.. (1996). Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer’s disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer’s disease. Nat. Med. 2: 864–870, https://doi.org/10.1038/nm0896-864.Search in Google Scholar

Schmid, B., Prehn, K.R., Nimsanor, N., Garcia, B.I.A., Poulsen, U., Jorring, I., Rasmussen, M.A., Clausen, C., Mau-Holzmann, U.A., Ramakrishna, S., et al.. (2019). Generation of a set of isogenic, gene-edited iPSC lines homozygous for all main APOE variants and an APOE knock-out line. Stem Cell Res. 34: 101349, https://doi.org/10.1016/j.scr.2018.11.010.Search in Google Scholar

Schoonenboom, N.S., Mulder, C., Van Kamp, G.J., Mehta, S.P., Scheltens, P., Blankenstein, M.A., and Mehta, P.D. (2005). Amyloid β 38, 40, and 42 species in cerebrospinal fluid: more of the same?. Ann. Neurol. 58: 139–142, https://doi.org/10.1002/ana.20508.Search in Google Scholar

Serrano-Pozo, A., Frosch, M.P., Masliah, E., and Hyman, B.T. (2011). Neuropathological alterations in Alzheimer disease. Cold Spring Harb. Perspect Med. 1: a006189, https://doi.org/10.1101/cshperspect.a006189.Search in Google Scholar

Shen, L. and Jia, J. (2016). An overview of genome-wide association studies in Alzheimer’s disease. Neurosci. Bull. 32: 183–190, https://doi.org/10.1007/s12264-016-0011-3.Search in Google Scholar

Shi, Y., Yamada, K., Liddelow, S.A., Smith, S.T., Zhao, L., Luo, W., Tsai, R.M., Spina, S., Grinberg, L.T., Rojas, J.C., et al.. (2017). ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy. Nature 549: 523–527, https://doi.org/10.1038/nature24016.Search in Google Scholar

Shirotani, K., Kondo, T., Asai, M., Tsukita, K., Watanabe, K., Maruyama, K., Murakami, K., Irie, K., Klein, W., Mori, H., et al.. (2013). Modeling Alzheimer’s disease using induced pluripotent stem cells from familial and sporadic Alzheimer’s disease patients. Alzheimers. Dement. 9: 184, https://doi.org/10.1016/j.jalz.2013.05.312.Search in Google Scholar

Shokri-Kojori, E., Wang, G.J., Wiers, C.E., Demiral, S.B., Guo, M., Kim, S.W., Lindgren, E., Ramirez, V., Zehra, A., Freeman, C., et al.. (2018). β-Amyloid accumulation in the human brain after one night of sleep deprivation. Proc. Natl. Acad. Sci. U. S. A. 115: 4483–4488, https://doi.org/10.1073/pnas.1721694115.Search in Google Scholar

Singh, V.K., Kalsan, M., Kumar, N., Saini, A., and Chandra, R. (2015). Induced pluripotent stem cells: applications in regenerative medicine, disease modeling, and drug discovery. Front Cell Dev. Biol. 3: 2, https://doi.org/10.3389/fcell.2015.00002.Search in Google Scholar

Spitzhorn, L.S., Megges, M., Wruck, W., Rahman, M.S., Otte, J., Degistirici, O., Meisel, R., Sorg, R.V., Oreffo, R.O.C., and Adjaye, J. (2019). Human iPSC-derived MSCs (iMSCs) from aged individuals acquire a rejuvenation signature. Stem Cell Res. Ther. 10: 100, https://doi.org/10.1186/s13287-019-1209-x.Search in Google Scholar

Sun, L., Zhou, R., Yang, G., and Shi, Y. (2017). Analysis of 138 pathogenic mutations in presenilin-1 on the in vitro production of Abeta42 and Abeta40 peptides by γ-secretase. Proc. Natl. Acad. Sci. U. S. A. 114: E476–E485, https://doi.org/10.1073/pnas.1618657114.Search in Google Scholar

Tamaoka, A. (1998). [Characterization of amyloid beta protein species in the plasma, cerebrospinal fluid and brains of patients with Alzheimer’s disease]. Nihon Ronen Igakkai Zasshi 35: 273–277, https://doi.org/10.3143/geriatrics.35.273.Search in Google Scholar

Tamaoka, A., Fukushima, T., Sawamura, N., Ishikawa, K.y., Oguni, E., Komatsuzaki, Y., and Shoji, S.i. (1996). Amyloid β protein in plasma from patients with sporadic Alzheimer’s disease. J. Neurol. Sci. 141: 65–68, https://doi.org/10.1016/0022-510x(96)00143-8.Search in Google Scholar

Tanzi, R.E. (2012). The genetics of Alzheimer disease. Cold Spring Harb. Perspect Med. 2, https://doi.org/10.1101/cshperspect.a006296.Search in Google Scholar

Tchieu, J., Calder, E.L., Guttikonda, S.R., Gutzwiller, E.M., Aromolaran, K.A., Steinbeck, J.A., Goldstein, P.A., and Studer, L. (2019). NFIA is a gliogenic switch enabling rapid derivation of functional human astrocytes from pluripotent stem cells. Nat. Biotechnol. 37: 267–275, https://doi.org/10.1038/s41587-019-0035-0.Search in Google Scholar

Tcw, J. and Goate, A.M. (2017). Genetics of beta-amyloid precursor protein in Alzheimer’s disease. ColdSpring Harb. Perspect. Med. 7: 600–614, https://doi.org/10.1101/cshperspect.a024539.Search in Google Scholar

Thordardottir, S., Kinhult Stahlbom, A., Almkvist, O., Thonberg, H., Eriksdotter, M., Zetterberg, H., Blennow, K., and Graff, C. (2017). The effects of different familial Alzheimer’s disease mutations on APP processing in vivo. Alzheimer’s Res. Ther. 9: 9, https://doi.org/10.1186/s13195-017-0234-1.Search in Google Scholar

Van Acker, Z.P., Bretou, M., and Annaert, W. (2019). Endo-lysosomal dysregulations and late-onset Alzheimer’s disease: impact of genetic risk factors. Mol. Neurodegener. 14: 20, https://doi.org/10.1186/s13024-019-0323-7.Search in Google Scholar

Van Cauwenberghe, C., Van Broeckhoven, C., and Sleegers, K. (2016). The genetic landscape of Alzheimer disease: clinical implications and perspectives. Genet. Med. 18: 421–430, https://doi.org/10.1038/gim.2015.117.Search in Google Scholar

van der Kant, R., Langness, V.F., Herrera, C.M., Williams, D.A., Fong, L.K., Leestemaker, Y., Steenvoorden, E., Rynearson, K.D., Brouwers, J.F., Helms, J.B., et al.. (2019). Cholesterol metabolism is a druggable Axis that independently regulates tau and amyloid-β in iPSC-derived Alzheimer’s disease neurons. Cell Stem Cell 24: 363–375, https://doi.org/10.1016/j.stem.2018.12.013.Search in Google Scholar

Varon, D., Loewenstein, D.A., Potter, E., Greig, M.T., Agron, J., Shen, Q., Zhao, W., Celeste Ramirez, M., Santos, I., Barker, W., et al.. (2011). Minimal atrophy of the entorhinal cortex and hippocampus: progression of cognitive impairment. Dement. Geriatr. Cognit. Disord. 31: 276–283, https://doi.org/10.1159/000324711.Search in Google Scholar

Verheyen, A., Diels, A., Dijkmans, J., Oyelami, T., Meneghello, G., Mertens, L., Versweyveld, S., Borgers, M., Buist, A., Peeters, P., and Cik, M. (2015). Using human iPSC-derived neurons to model TAU aggregation. PLoS One 10: e0146127, https://doi.org/10.1371/journal.pone.0146127.Search in Google Scholar

Wang, J.Z., Xia, Y.Y., Grundke-Iqbal, I., and Iqbal, K. (2013). Abnormal hyperphosphorylation of tau: sites, regulation, and molecular mechanism of neurofibrillary degeneration. J. Alzheimers Dis. 33: S123–S139. https://doi.org/10.3233/jad-2012-129031.Search in Google Scholar

Woodruff, G., Reyna, S.M., Dunlap, M., Van Der Kant, R., Callender, J.A., Young, J.E., Roberts, E.A., and Goldstein, L.S. (2016). Defective transcytosis of APP and lipoproteins in human iPSC-derived neurons with familial Alzheimer’s disease mutations. Cell Rep. 17: 759–773, https://doi.org/10.1016/j.celrep.2016.09.034.Search in Google Scholar

Woodruff, G., Young, J.E., Martinez, F.J., Buen, F., Gore, A., Kinaga, J., Li, Z., Yuan, S.H., Zhang, K., and Goldstein, L.S. (2013). The presenilin-1 ΔE9 mutation results in reduced gamma-secretase activity, but not total loss of PS1 function, in isogenic human stem cells. Cell Rep. 5: 974–985, https://doi.org/10.1016/j.celrep.2013.10.018.Search in Google Scholar

Wu, L., Zhang, X., and Zhao, L. (2018). Human ApoE isoforms differentially modulate brain glucose and ketone body metabolism: implications for Alzheimer’s disease risk reduction and early intervention. J. Neurosci. 38: 6665–6681, https://doi.org/10.1523/jneurosci.2262-17.2018.Search in Google Scholar

Xia, D., Watanabe, H., Wu, B., Lee, S.H., Li, Y., Tsvetkov, E., Bolshakov, V.Y., Shen, J., and Kelleher, R.J.3rd. (2015). Presenilin-1 knockin mice reveal loss-of-function mechanism for familial Alzheimer’s disease. Neuron 85: 967–981, https://doi.org/10.1016/j.neuron.2015.02.010.Search in Google Scholar

Xu, H.R., Li, T., Guo, Y., Li, H.F., Wang, L., Zhang, Z.Y., and Wang, X. (2015). Efficient assembly and verification of ZFNs and TALENs for modifying porcine ApoE gene. BioRxiv, https://doi.org/10.1101/013714 013714.10.1101/013714Search in Google Scholar

Xu, M., Zhang, L., Liu, G., Jiang, N., Zhou, W., and Zhang, Y. (2019). Pathological changes in Alzheimer’s disease Analyzed using induced pluripotent stem cell-derived human microglia-like cells. J. Alzheimers Dis. 67: 357–368, https://doi.org/10.3233/jad-180722.Search in Google Scholar

Yagi, T., Ito, D., Okada, Y., Akamatsu, W., Nihei, Y., Yoshizaki, T., Yamanaka, S., Okano, H., and Suzuki, N. (2011). Modeling familial Alzheimer’s disease with induced pluripotent stem cells. Hum. Mol. Genet. 20: 4530–4539, https://doi.org/10.1093/hmg/ddr394.Search in Google Scholar

Yang, J., Zhao, H., Ma, Y., Shi, G., Song, J., Tang, Y., Li, S., Li, T., Liu, N., Tang, F., Gu, J., Zhang, L., Zhang, Z., Zhang, X., Jin, Y., and Le, W. (2017). Early pathogenic event of Alzheimer’s disease documented in iPSCs from patients with PSEN1 mutations. Oncotarget 8: 7900–7913, https://doi.org/10.18632/oncotarget.13776.Search in Google Scholar

Young, J.E., Boulanger-Weill, J., Williams, D.A., Woodruff, G., Buen, F., Revilla, A.C., Herrera, C., Israel, M.A., Yuan, S.H., Edland, S.D., et al.. (2015). Elucidating molecular phenotypes caused by the SORL1 Alzheimer’s disease genetic risk factor using human induced pluripotent stem cells. Cell Stem Cell 16: 373–385, https://doi.org/10.1016/j.stem.2015.02.004.Search in Google Scholar

Zhang, D., Pekkanen-Mattila, M., Shahsavani, M., Falk, A., Teixeira, A.I., and Herland, A. (2014). A 3D Alzheimer’s disease culture model and the induction of P21-activated kinase mediated sensing in iPSC derived neurons. Biomaterials 35: 1420–1428, https://doi.org/10.1016/j.biomaterials.2013.11.028.Search in Google Scholar

Zhang, Q. and Austin, R.H. (2012). Applications of microfluidics in stem cell biology. BioNanoScience 2: 277–286, https://doi.org/10.1007/s12668-012-0051-8.Search in Google Scholar

Zhao, J., Davis, M.D., Martens, Y.A., Shinohara, M., Graff-Radford, N.R., Younkin, S.G., Wszolek, Z.K., Kanekiyo, T., and Bu, G. (2017). APOE ε4/ε4 diminishes neurotrophic function of human iPSC-derived astrocytes. Hum. Mol. Genet. 26: 2690–2700, https://doi.org/10.1093/hmg/ddx155.Search in Google Scholar

Zhou, M., Huang, T., Collins, N., Zhang, J., Shen, H., Dai, X., Xiao, N., Wu, X., Wei, Z., York, J., et al.. (2016). APOE4 induces site-specific tau phosphorylation through calpain-CDK5 signaling pathway in EFAD-Tg mice. Curr. Alzheimer Res. 13: 1048–1055, https://doi.org/10.2174/1567205013666160415154550.Search in Google Scholar

Zhu, L., Sun, C., Ren, J., Wang, G., Ma, R., Sun, L., Yang, D., Gao, S., Ning, K., Wang, Z., et al.. (2019). Stress-induced precocious aging in PD-patient iPSC-derived NSCs may underlie the pathophysiology of Parkinson’s disease. Cell Death Dis. 10: 105, https://doi.org/10.1038/s41419-019-1313-y.Search in Google Scholar

Zhu, L., Zhong, M., Elder, G.A., Sano, M., Holtzman, D.M., Gandy, S., Cardozo, C., Haroutunian, V., Robakis, N.K., and Cai, D. (2015). Phospholipid dysregulation contributes to ApoE4-associated cognitive deficits in Alzheimer’s disease pathogenesis. Proc. Natl. Acad. Sci. U.S.A. 112: 11965–11970, https://doi.org/10.1073/pnas.1510011112.Search in Google Scholar

Zollo, A., Allen, Z., Rasmussen, H.F., Iannuzzi, F., Shi, Y., Larsen, A., Maier, T.J., and Matrone, C. (2017). Sortilin-related receptor expression in human neural stem cells derived from Alzheimer’s disease patients carrying the APOE epsilon 4 allele. Neural Plast. 2017: 1892612, https://doi.org/10.1155/2017/1892612.Search in Google Scholar