Human iPSC-Derived Hippocampal Spheroids: An Innovative Tool for Stratifying Alzheimer Disease Patient-Specific Cellular Phenotypes and Developing Therapies
Open accessAbstract
The hippocampus is important for memory formation and is severely affected in the brain with Alzheimer disease (AD). Our understanding of early pathogenic processes occurring in hippocampi in AD is limited due to tissue unavailability. Here, we report a chemical approach to rapidly generate free-floating hippocampal spheroids (HSs), from human induced pluripotent stem cells. When used to model AD, both APP and atypical PS1 variant HSs displayed increased Aβ42/Aβ40 peptide ratios and decreased synaptic protein levels, which are common features of AD. However, the two variants differed in tau hyperphosphorylation, protein aggregation, and protein network alterations. NeuroD1-mediated gene therapy in HSs-derived progenitors resulted in modulation of expression of numerous genes, including those involved in synaptic transmission. Thus, HSs can be harnessed to unravel the mechanisms underlying early pathogenic changes in the hippocampi of AD patients, and provide a robust platform for the development of therapeutic strategies targeting early stage AD.
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There are sex-related susceptibilities to developing AD and immune responses.
“According to recent studies, there are sex-related susceptibilities to developing AD and immune responses [65].”
From Emerging Role of miR-21-5p in Neuron–Glia Dysregulation and Exosome Transfer Using Multiple Models of Alzheimer’s Disease (2022) · cites this paper as [65]
The Results section on quantitative proteomics reports that hippocampal spheroid samples segregated by donor gender and suggests gender-specific comparisons when analyzing disease phenotypes; no page number is available in our copy. That does not establish sex-related susceptibility to developing AD or differences in immune responses. Searches for sex-related AD risk and immune responses found no passage addressing either claim. (LLM, conf=0.72)
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Cites
Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling
Chambers, S. M., Fasano, C. A., Papapetrou, E. P., Tomishima, M., Sadelain, M., & Studer, L. (2009) · Nature Biotechnology · doi:10.1038/nbt.1529 · Cited by 3,620 · see citing works
Modeling Development and Disease with Organoids
Clevers, H. (2016) · Cell · doi:10.1016/j.cell.2016.05.082 · Cited by 3,196 · see citing works
The role of apolipoprotein E in Alzheimer's disease
Kim, J., Basak, J. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.06.026 · Cited by 1,661 · see citing works
Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture
Paşca, A. M., Sloan, S. A., Clarke, L. E., Tian, Y., Makinson, C. D., Huber, N., Kim, C. H., Park, J.-Y., O'Rourke, N. A., Nguyen, K. D., et al. (2015) · Nature Methods · doi:10.1038/nmeth.3415 · Cited by 1,609 · see citing works
Probing sporadic and familial Alzheimer’s disease using induced pluripotent stem cells
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., et al. (2012) · Nature · doi:10.1038/nature10821 · Cited by 1,253 · see citing works
Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons
Nagai, M., Re, D. B., Nagata, T., Chalazonitis, A., Jessell, T. M., Wichterle, H., & Przedborski, S. (2007) · Nature Neuroscience · doi:10.1038/nn1876 · Cited by 1,220 · see citing works
Ageing, neurodegeneration and brain rejuvenation
Wyss-Coray, T. (2016) · Nature · doi:10.1038/nature20411 · Cited by 1,147 · see citing works
Cogswell, J. P., Ward, J., Taylor, I. A., Waters, M., Shi, Y., Cannon, B., Kelnar, K., Kemppainen, J., Brown, D., Chen, C., et al. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-14103 · Cited by 943 · see citing works
Kondo, T., Asai, M., Tsukita, K., Kutoku, Y., Ohsawa, Y., Sunada, Y., Imamura, K., Egawa, N., Yahata, N., Okita, K., et al. (2013) · Cell Stem Cell · doi:10.1016/j.stem.2013.01.009 · Cited by 741 · see citing works
Monoclonal antibody AT8 recognises tau protein phosphorylated at both serine 202 and threonine 205
Goedert, M., Jakes, R., & Vanmechelen, E. (1995) · Neuroscience Letters · doi:10.1016/0304-3940(95)11484-e · Cited by 608 · see citing works
Sloan, S. A., Darmanis, S., Huber, N., Khan, T. A., Birey, F., Caneda, C., Reimer, R., Quake, S. R., Barres, B. A., & Paşca, S. P. (2017) · Neuron · doi:10.1016/j.neuron.2017.07.035 · Cited by 593 · see citing works
Sakaguchi, H., Kadoshima, T., Soen, M., Narii, N., Ishida, Y., Ohgushi, M., Takahashi, J., Eiraku, M., & Sasai, Y. (2015) · Nature Communications · doi:10.1038/ncomms9896 · Cited by 542 · see citing works
Kuperstein, I., Broersen, K., Benilova, I., Rozenski, J., Jonckheere, W., Debulpaep, M., Vandersteen, A., Segers‐Nolten, I., Van Der Werf, K., Subramaniam, V., et al. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.211 · Cited by 532 · see citing works
Inconsistencies and Controversies Surrounding the Amyloid Hypothesis of Alzheimer's Disease
Morris, G. P., Clark, I. A., & Vissel, B. (2014) · Acta Neuropathologica Communications · doi:10.1186/s40478-014-0135-5 · Cited by 522 · see citing works
Beta-amyloid accumulation in APP mutant neurons reduces PSD-95 and GluR1 in synapses
Almeida, C. G., Tampellini, D., Takahashi, R. H., Greengard, P., Lin, M. T., Snyder, E. M., & Gouras, G. K. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.02.008 · Cited by 397 · see citing works
Self-citationHDAC6 inhibition reverses axonal transport defects in motor neurons derived from FUS-ALS patients
Guo, W., Naujock, M., Fumagalli, L., Vandoorne, T., Baatsen, P., Boon, R., Ordovás, L., Patel, A., Welters, M., Vanwelden, T., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00911-y · Cited by 373 · see citing works
PSEN1 Mutant iPSC-Derived Model Reveals Severe Astrocyte Pathology in Alzheimer's Disease
Oksanen, M., Petersen, A. J., Naumenko, N., Puttonen, K., Lehtonen, Š., Gubert Olivé, M., Shakirzyanova, A., Leskelä, S., Sarajärvi, T., Viitanen, M., et al. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.10.016 · Cited by 332 · see citing works
The HD iPSC Consortium, Lim, R. G., Salazar, L. L., Wilton, D. K., King, A. R., Stocksdale, J. T., Sharifabad, D., Lau, A. L., Stevens, B., Reidling, J. C., et al. (2017) · Nature Neuroscience · doi:10.1038/nn.4532 · Cited by 221 · see citing works
Human Stem Cell-Derived Spinal Cord Astrocytes with Defined Mature or Reactive Phenotypes
Roybon, L., Lamas, N. J., Garcia-Diaz, A., Yang, E. J., Sattler, R., Jackson-Lewis, V., Kim, Y. A., Kachel, C. A., Rothstein, J. D., Przedborski, S., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.06.021 · Cited by 208 · see citing works
Self-citationCellular phenotypes in human iPSC-derived neurons from a genetic model of autism spectrum disorder
Deshpande, A., Yadav, S., Dao, D. Q., Wu, Z.-Y., Hokanson, K. C., Cahill, M. K., Wiita, A. P., Jan, Y.-N., Ullian, E. M., & Weiss, L. A. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.11.037 · Cited by 151 · see citing works
Stem cell models of Alzheimer’s disease: progress and challenges
Arber, C., Lovejoy, C., & Wray, S. (2017) · Alzheimer's Research & Therapy · doi:10.1186/s13195-017-0268-4 · Cited by 143 · see citing works
Flagged first, then by citations
Research works printed but not linked: 64
- Abellan A. Desfilis E. Medina L. Combinatorial expression of Lef1, Lhx2, Lhx5, Lhx9, Lmo3, Lmo4, and Prox1 helps to identify comparable subdivisions in the developing hippocampal formation of mouse and chicken Front. Neuroanat. 8 2014 59 25071464 PMC4082316
- An F. Gong G. Wang Y. Bian M. Yu L. Wei C. MiR-124 acts as a target for Alzheimer's disease by regulating BACE1 Oncotarget 8 2017 114065 114071 29371969 PMC5768386
- Assini A. Terreni L. Borghi R. Giliberto L. Piccini A. Loqui D. Fogliarino S. Forloni G. Tabaton M. Pure spastic paraparesis associated with a novel presenilin 1 R278K mutation Neurology 60 2003 150 12525746
- Baker M.J. Trevisan J. Bassan P. Bhargava R. Butler H.J. Dorling K.M. Fielden P.R. Fogarty S.W. Fullwood N.J. Heys K.A. Using Fourier transform IR spectroscopy to analyze biological materials Nat. Protoc. 9 2014 1771 1791 24992094 PMC4480339
- Banzhaf-Strathmann J. Benito E. May S. Arzberger T. Tahirovic S. Kretzschmar H. Fischer A. Edbauer D. MicroRNA-125b induces tau hyperphosphorylation and cognitive deficits in Alzheimer's disease EMBO J. 33 2014 1667 1680 25001178 PMC4194100
- Barth A. Kreutz W. Mantele W. Changes of protein structure, nucleotide microenvironment, and Ca(2+)-binding states in the catalytic cycle of sarcoplasmic reticulum Ca(2+)-ATPase: investigation of nucleotide binding, phosphorylation and phosphoenzyme conversion by FTIR difference spectroscopy Biochim. Biophys. Acta 1194 1994 75 91 8075144
- Baum L. Chen L. Masliah E. Chan Y.S. Ng H.K. Pang C.P. Lipoprotein lipase mutations and Alzheimer's disease Am. J. Med. Genet. 88 1999 136 139 10206232
- Boutet C. Chupin M. Lehericy S. Marrakchi-Kacem L. Epelbaum S. Poupon C. Wiggins C. Vignaud A. Hasboun D. Defontaines B. Detection of volume loss in hippocampal layers in Alzheimer's disease using 7 T MRI: a feasibility study Neuroimage Clin. 5 2014 341 348 25161900 PMC4141975
- Bull N.D. Bartlett P.F. The adult mouse hippocampal progenitor is neurogenic but not a stem cell J. Neurosci. 25 2005 10815 10821 16306394 PMC6725873
- Butz S. Okamoto M. Sudhof T.C. A tripartite protein complex with the potential to couple synaptic vesicle exocytosis to cell adhesion in brain Cell 94 1998 773 782 9753324
- Chen J.K. Taipale J. Cooper M.K. Beachy P.A. Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened Genes Dev. 16 2002 2743 2748 12414725 PMC187469
- Dangla-Valls A. Molinuevo J.L. Altirriba J. Sanchez-Valle R. Alcolea D. Fortea J. Rami L. Balasa M. Munoz-Garcia C. Ezquerra M. CSF microRNA profiling in Alzheimer's disease: a screening and validation study Mol. Neurobiol. 54 2017 6647 6654 27738874
- de Wilde M.C. Overk C.R. Sijben J.W. Masliah E. Meta-analysis of synaptic pathology in Alzheimer's disease reveals selective molecular vesicular machinery vulnerability Alzheimers Dement. 12 2016 633 644 26776762 PMC5058345
- Dimos J.T. Rodolfa K.T. Niakan K.K. Weisenthal L.M. Mitsumoto H. Chung W. Croft G.F. Saphier G. Leibel R. Goland R. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons Science 321 2008 1218 1221 18669821
- Djelloul M. Holmqvist S. Boza-Serrano A. Azevedo C. Yeung M.S. Goldwurm S. Frisen J. Deierborg T. Roybon L. Alpha-synuclein expression in the oligodendrocyte lineage: an in vitro and in vivo study using rodent and human models Stem Cell Reports 5 2015 174 184 26235891 PMC4618831
- Duering M. Grimm M.O. Grimm H.S. Schroder J. Hartmann T. Mean age of onset in familial Alzheimer's disease is determined by amyloid beta 42 Neurobiol. Aging 26 2005 785 788 15718035
- Forner S. Baglietto-Vargas D. Martini A.C. Trujillo-Estrada L. LaFerla F.M. Synaptic impairment in Alzheimer's disease: a dysregulated symphony Trends Neurosci. 40 2017 347 357 28494972
- Fujimori K. Ishikawa M. Otomo A. Atsuta N. Nakamura R. Akiyama T. Hadano S. Aoki M. Saya H. Sobue G. Modeling sporadic ALS in iPSC-derived motor neurons identifies a potential therapeutic agent Nat. Med. 24 2018 1579 1589 30127392
- He X.Y. Isaacs C. Yang S.Y. Roles of mitochondrial 17beta-hydroxysteroid dehydrogenase type 10 in Alzheimer's disease J. Alzheimers Dis. 62 2018 665 673 29480196
- Hebert S.S. Horre K. Nicolai L. Bergmans B. Papadopoulou A.S. Delacourte A. De Strooper B. MicroRNA regulation of Alzheimer's amyloid precursor protein expression Neurobiol. Dis. 33 2009 422 428 19110058
- Hebert S.S. Horre K. Nicolai L. Papadopoulou A.S. Mandemakers W. Silahtaroglu A.N. Kauppinen S. Delacourte A. De Strooper B. Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer's disease correlates with increased BACE1/beta-secretase expression Proc. Natl. Acad. Sci. U S A 105 2008 6415 6420 18434550 PMC2359789
- Ho R. Sances S. Gowing G. Amoroso M.W. O'Rourke J.G. Sahabian A. Wichterle H. Baloh R.H. Sareen D. Svendsen C.N. ALS disrupts spinal motor neuron maturation and aging pathways within gene co-expression networks Nat. Neurosci. 19 2016 1256 1267 27428653 PMC5003654
- Holmqvist S. Lehtonen S. Chumarina M. Puttonen K.A. Azevedo C. Lebedeva O. Ruponen M. Oksanen M. Djelloul M. Collin A. Creation of a library of induced pluripotent stem cells from Parkinsonian patients NPJ Parkinsons Dis. 2 2016 16009 28725696 PMC5516589
- Jin M. Shepardson N. Yang T. Chen G. Walsh D. Selkoe D.J. Soluble amyloid beta-protein dimers isolated from Alzheimer cortex directly induce Tau hyperphosphorylation and neuritic degeneration Proc. Natl. Acad. Sci. U S A 108 2011 5819 5824 21421841 PMC3078381
- Jones V.C. Atkinson-Dell R. Verkhratsky A. Mohamet L. Aberrant iPSC-derived human astrocytes in Alzheimer's disease Cell Death Dis. 8 2017 e2696 28333144 PMC5386580
- Klementieva O. Willen K. Martinsson I. Israelsson B. Engdahl A. Cladera J. Uvdal P. Gouras G.K. Pre-plaque conformational changes in Alzheimer's disease-linked Abeta and APP Nat. Commun. 8 2017 14726 28287086 PMC5355803
- 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. PSEN1DeltaE9, APPswe, and APOE4 confer disparate phenotypes in human iPSC-derived microglia Stem Cell Reports 13 2019 669 683 31522977 PMC6829767
- Konttinen H. Gureviciene I. Oksanen M. Grubman A. Loppi S. Huuskonen M.T. Korhonen P. Lampinen R. Keuters M. Belaya I. PPARbeta/delta-agonist GW0742 ameliorates dysfunction in fatty acid oxidation in PSEN1DeltaE9 astrocytes Glia 67 2019 146 159 30453390 PMC7526864
- Lavado A. Oliver G. Prox1 expression patterns in the developing and adult murine brain Dev. Dyn. 236 2007 518 524 17117441
- Leidinger P. Backes C. Deutscher S. Schmitt K. Mueller S.C. Frese K. Haas J. Ruprecht K. Paul F. Stahler C. A blood based 12-miRNA signature of Alzheimer disease patients Genome Biol. 14 2013 R78 23895045 PMC4053778
- Lukiw W.J. Micro-RNA speciation in fetal, adult and Alzheimer's disease hippocampus Neuroreport 18 2007 297 300 17314675
- Madhavan M. Nevin Z.S. Shick H.E. Garrison E. Clarkson-Paredes C. Karl M. Clayton B.L.L. Factor D.C. Allan K.C. Barbar L. Induction of myelinating oligodendrocytes in human cortical spheroids Nat. Methods 15 2018 700 706 30046099 PMC6508550
- Mandelkow E.M. Mandelkow E. Biochemistry and cell biology of tau protein in neurofibrillary degeneration Cold Spring Harb. Perspect. Med. 2 2012 a006247 22762014 PMC3385935
- Mansour A.A. Goncalves J.T. Bloyd C.W. Li H. Fernandes S. Quang D. Johnston S. Parylak S.L. Jin X. Gage F.H. An in vivo model of functional and vascularized human brain organoids Nat. Biotechnol. 36 2018 432 441 29658944 PMC6331203
- Mitew S. Kirkcaldie M.T. Halliday G.M. Shepherd C.E. Vickers J.C. Dickson T.C. Focal demyelination in Alzheimer's disease and transgenic mouse models Acta Neuropathol. 119 2010 567 577 20198482
- Miya Shaik M. Tamargo I.A. Abubakar M.B. Kamal M.A. Greig N.H. Gan S.H. The role of microRNAs in Alzheimer's disease and their therapeutic potentials Genes (Basel) 9 2018 10.3390/genes9040174 PMC5924516 29561798 · DOI
- Mueller S.G. Schuff N. Yaffe K. Madison C. Miller B. Weiner M.W. Hippocampal atrophy patterns in mild cognitive impairment and Alzheimer's disease Hum. Brain Mapp. 31 2010 1339 1347 20839293 PMC2943433
- Muratore C.R. Rice H.C. Srikanth P. Callahan D.G. Shin T. Benjamin L.N. Walsh D.M. Selkoe D.J. Young-Pearse T.L. The familial Alzheimer's disease APPV717I mutation alters APP processing and Tau expression in iPSC-derived neurons Hum. Mol. Genet. 23 2014 3523 3536 24524897 PMC4049307
- Murphy M.P. LeVine H. 3rd Alzheimer's disease and the amyloid-beta peptide J. Alzheimers Dis. 19 2010 311 323 20061647 PMC2813509
- Nasrabady S.E. Rizvi B. Goldman J.E. Brickman A.M. White matter changes in Alzheimer's disease: a focus on myelin and oligodendrocytes Acta Neuropathol. Commun. 6 2018 22 29499767 PMC5834839
- Nicoleau C. Varela C. Bonnefond C. Maury Y. Bugi A. Aubry L. Viegas P. Bourgois-Rocha F. Peschanski M. Perrier A.L. Embryonic stem cells neural differentiation qualifies the role of Wnt/beta-Catenin signals in human telencephalic specification and regionalization Stem Cells 31 2013 1763 1774 23818270
- Nielsen J.V. Thomassen M. Mollgard K. Noraberg J. Jensen N.A. Zbtb20 defines a hippocampal neuronal identity through direct repression of genes that control projection neuron development in the isocortex Cereb. Cortex 24 2014 1216 1229 23283686
- Ovchinnikov D.A. Korn O. Virshup I. Wells C.A. Wolvetang E.J. The impact of APP on Alzheimer-like pathogenesis and gene expression in Down syndrome iPSC-derived neurons Stem Cell Reports 11 2018 32 42 29861166 PMC6066957
- Richetin K. Leclerc C. Toni N. Gallopin T. Pech S. Roybon L. Rampon C. Genetic manipulation of adult-born hippocampal neurons rescues memory in a mouse model of Alzheimer's disease Brain 138 2015 440 455 25518958
- Richetin K. Moulis M. Millet A. Arrazola M.S. Andraini T. Hua J. Davezac N. Roybon L. Belenguer P. Miquel M.C. Amplifying mitochondrial function rescues adult neurogenesis in a mouse model of Alzheimer's disease Neurobiol. Dis. 102 2017 113 124 28286181
- Richetin K. Petsophonsakul P. Roybon L. Guiard B.P. Rampon C. Differential alteration of hippocampal function and plasticity in females and males of the APPxPS1 mouse model of Alzheimer's disease Neurobiol. Aging 57 2017 220 231 28666707
- Roybon L. Deierborg T. Brundin P. Li J.Y. Involvement of Ngn2, Tbr and NeuroD proteins during postnatal olfactory bulb neurogenesis Eur. J. Neurosci. 29 2009 232 243 19200230
- Roybon L. Hjalt T. Stott S. Guillemot F. Li J.Y. Brundin P. Neurogenin2 directs granule neuroblast production and amplification while NeuroD1 specifies neuronal fate during hippocampal neurogenesis PLoS One 4 2009 e4779 19274100 PMC2652712
- Roybon L. Mastracci T.L. Li J. Stott S.R. Leiter A.B. Sussel L. Brundin P. Li J.Y. The origin, development and molecular diversity of rodent olfactory bulb glutamatergic neurons distinguished by expression of transcription factor NeuroD1 PLoS One 10 2015 e0128035 26030886 PMC4451148
- Sarkar A. Mei A. Paquola A.C.M. Stern S. Bardy C. Klug J.R. Kim S. Neshat N. Kim H.J. Ku M. Efficient generation of CA3 neurons from human pluripotent stem cells enables modeling of hippocampal connectivity in vitro Cell Stem Cell 22 2018 684 697.e9 29727680 PMC6345574
- Saura C.A. Parra-Damas A. Enriquez-Barreto L. Gene expression parallels synaptic excitability and plasticity changes in Alzheimer's disease Front. Cell Neurosci 9 2015 318 26379494 PMC4548151
- Scheff S.W. Neltner J.H. Nelson P.T. Is synaptic loss a unique hallmark of Alzheimer's disease? Biochem. Pharmacol. 88 2014 517 528 24412275 PMC4230706
- Schuff N. Woerner N. Boreta L. Kornfield T. Shaw L.M. Trojanowski J.Q. Thompson P.M. Jack C.R. Jr. Weiner M.W. Alzheimer's Disease Neuroimaging I. MRI of hippocampal volume loss in early Alzheimer's disease in relation to ApoE genotype and biomarkers Brain 132 2009 1067 1077 19251758 PMC2668943
- Shioya M. Obayashi S. Tabunoki H. Arima K. Saito Y. Ishida T. Satoh J. Aberrant microRNA expression in the brains of neurodegenerative diseases: miR-29a decreased in Alzheimer disease brains targets neurone navigator 3 Neuropathol. Appl. Neurobiol. 36 2010 320 330 20202123
- Siebzehnrubl F.A. Raber K.A. Urbach Y.K. Schulze-Krebs A. Canneva F. Moceri S. Habermeyer J. Achoui D. Gupta B. Steindler D.A. Early postnatal behavioral, cellular, and molecular changes in models of Huntington disease are reversible by HDAC inhibition Proc. Natl. Acad. Sci. U S A. 115 2018 E8765 E8774 30150378 PMC6140493
- Sorbi S. Nacmias B. Forleo P. Piacentini S. Amaducci L. Provinciali L. APP717 and Alzheimer's disease in Italy Nat. Genet. 4 1993 10 8513318
- Tampellini D. Capetillo-Zarate E. Dumont M. Huang Z. Yu F. Lin M.T. Gouras G.K. Effects of synaptic modulation on beta-amyloid, synaptophysin, and memory performance in Alzheimer's disease transgenic mice J. Neurosci. 30 2010 14299 14304 20980585 PMC2972675
- Venegas C. Kumar S. Franklin B.S. Dierkes T. Brinkschulte R. Tejera D. Vieira-Saecker A. Schwartz S. Santarelli F. Kummer M.P. Microglia-derived ASC specks cross-seed amyloid-beta in Alzheimer's disease Nature 552 2017 355 361 29293211
- Watanabe K. Kamiya D. Nishiyama A. Katayama T. Nozaki S. Kawasaki H. Watanabe Y. Mizuseki K. Sasai Y. Directed differentiation of telencephalic precursors from embryonic stem cells Nat. Neurosci. 8 2005 288 296 15696161
- Woodard C.M. Campos B.A. Kuo S.H. Nirenberg M.J. Nestor M.W. Zimmer M. Mosharov E.V. Sulzer D. Zhou H. Paull D. iPSC-derived dopamine neurons reveal differences between monozygotic twins discordant for Parkinson's disease Cell Rep. 9 2014 1173 1182 25456120 PMC4255586
- Woodruff G. Reyna S.M. Dunlap M. Van Der Kant R. Callender J.A. Young J.E. Roberts E.A. Goldstein L.S. Defective transcytosis of APP and lipoproteins in human iPSC-derived neurons with familial Alzheimer's disease mutations Cell Rep 17 2016 759 773 27732852 PMC5796664
- Yamakawa H. Cheng J. Penney J. Gao F. Rueda R. Wang J. Yamakawa S. Kritskiy O. Gjoneska E. Tsai L.H. The transcription factor Sp3 cooperates with HDAC2 to regulate synaptic function and plasticity in neurons Cell Rep. 20 2017 1319 1334 28793257
- Yu D.X. Di Giorgio F.P. Yao J. Marchetto M.C. Brennand K. Wright R. Mei A. McHenry L. Lisuk D. Grasmick J.M. Modeling hippocampal neurogenesis using human pluripotent stem cells Stem Cell Reports 2 2014 295 310 24672753 PMC3964286
- Zhao T. Fu Y. Zhu J. Liu Y. Zhang Q. Yi Z. Chen S. Jiao Z. Xu X. Xu J. Single-cell RNA-seq reveals dynamic early embryonic-like programs during chemical reprogramming Cell Stem Cell 23 2018 31 45 e37 29937202
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Garcia, G., Pinto, S., Ferreira, S., Lopes, D., Serrador, M. J., Fernandes, A., Vaz, A. R., Mendonça, A. D., Edenhofer, F., Malm, T., et al. (2022) · Cells · doi:10.3390/cells11213377 · Cited by 55 · see citing works
“According to recent studies, there are sex-related susceptibilities to developing AD and immune responses [65].”
BackgroundSelf-citation
- Authors
- Pomeshchik, Y., Klementieva, O., Gil, J., Martinsson, I., Hansen, M. G., de Vries, T., Sancho-Balsells, A., Russ, K., Savchenko, E., Collin, A., Vaz, A. R., Bagnoli, S., Nacmias, B., Rampon, C., Sorbi, S., Brites, D., Marko-Varga, G., Kokaia, Z., Rezeli, M., Gouras, G. K., & Roybon, L.
- Affiliations
- Lund University (SE)
- University of Lisbon (PT)
- Don Carlo Gnocchi Foundation (IT)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Roybon, Laurent
- ORCID
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- Stem Cell Reports
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- Elsevier BV
- Published
- 2020-07
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- 15
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- 1
- Pages
- 256-273
- ISSN
- 2213-6711 (ISSN-L)
- PMC
- PMC7363942
- OpenAlex
- W3037614667
- Cited by
- 95
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- 21
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- en
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- Funders
- Fundação para a Ciência e a Tecnologia (2015-06797, JPco-fuND/0003/2015, SFRH/BPD/76590/2011, UID/DTP/04138/2013)
- Kungliga Fysiografiska Sällskapet i Lund
- Fondazione Telethon
- Suomen Kulttuurirahasto
- Lunds Universitet
- Allen Foundation
- Hjärnfonden
- EU Joint Programme – Neurodegenerative Disease Research
- Vetenskapsrådet
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- Alzheimer's disease, human induced pluripotent stem cells, APP, amyloid-beta 42/40 ratio, tau hyperphosphorylation, synaptic proteins, protein aggregation, disease modeling, early Alzheimer's disease
- MeSH terms
- Alzheimer Disease, Hippocampus, Humans, Neurons, Phenotype, Transcription, Genetic, Genetic Therapy, Case-Control Studies, Amyloid beta-Protein Precursor, Spheroids, Cellular, Proteome, Proteomics, Presenilin-1, Induced Pluripotent Stem Cells, Protein Aggregates
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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