The DOI matches its Crossref record; 73 of the 73 references it cites were found in a registry or an index.
Stem cell-derived neurons reflect features of protein networks, neuropathology, and cognitive outcome of their aged human donors
Open accessAbstract
We have generated a controlled and manipulable resource that captures genetic risk for Alzheimer's disease: iPSC lines from 53 individuals coupled with RNA and proteomic profiling of both iPSC-derived neurons and brain tissue of the same individuals. Data collected for each person include genome sequencing, longitudinal cognitive scores, and quantitative neuropathology. The utility of this resource is exemplified here by analyses of neurons derived from these lines, revealing significant associations between specific Aβ and tau species and the levels of plaque and tangle deposition in the brain and, more importantly, with the trajectory of cognitive decline. Proteins and networks are identified that are associated with AD phenotypes in iPSC neurons, and relevant associations are validated in brain. The data presented establish this iPSC collection as a resource for investigating person-specific processes in the brain that can aid in identifying and validating molecular pathways underlying AD.
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“We detected several SHIP1 binding partners previously identified in other myeloid cells, such as SH3KBP117, GRB218, SHC118, DOK218,19, ARAP120 and CD2AP21 (Figure 1D).”
From INPP5D/SHIP1 regulates endo-lysosomal function and cargo-selective phagocytosis in human microglia (2025) · cites this paper as [17]
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Cites
Fiji: an open-source platform for biological-image analysis
Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Rueden, C., Saalfeld, S., Schmid, B., et al. (2012) · Nature Methods · doi:10.1038/nmeth.2019 · Cited by 66,890
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
WGCNA: an R package for weighted correlation network analysis
Langfelder, P., & Horvath, S. (2008) · BMC Bioinformatics · doi:10.1186/1471-2105-9-559 · Cited by 27,252
Cox, J., & Mann, M. (2008) · Nature Biotechnology · doi:10.1038/nbt.1511 · Cited by 14,855
Structuring and extracting knowledge for the support of hypothesis generation in molecular biology
Roos, M., Marshall, M. S., Gibson, A. P., Schuemie, M., Meij, E., Katrenko, S., van Hage, W. V., Krommydas, K., & Adriaans, P. (2009) · BMC Bioinformatics · doi:10.1186/1471-2105-10-s10-s9 · Cited by 11,123
Mootha, V. K., Lindgren, C. M., Eriksson, K.-F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstråle, M., Laurila, E., et al. (2003) · Nature Genetics · doi:10.1038/ng1180 · Cited by 10,197
Near-optimal probabilistic RNA-seq quantification
Bray, N. L., Pimentel, H., Melsted, P., & Pachter, L. (2016) · Nature Biotechnology · doi:10.1038/nbt.3519 · Cited by 9,723
Adjusting batch effects in microarray expression data using empirical Bayes methods
Johnson, W. E., Li, C., & Rabinovic, A. (2007) · Biostatistics · doi:10.1093/biostatistics/kxj037 · Cited by 8,658
The amyloid hypothesis of Alzheimer's disease at 25 years
Selkoe, D. J., & Hardy, J. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201606210 · Cited by 6,164
Self-citationTerry, R. D., Masliah, E., Salmon, D. P., Butters, N., DeTeresa, R., Hill, R., Hansen, L. A., & Katzman, R. (1991) · Annals of Neurology · doi:10.1002/ana.410300410 · Cited by 4,397
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Research works printed but not linked: 1
- Garcia-Esparcia, 2017, Altered mechanisms of protein synthesis in frontal cortex in Alzheimer disease and a mouse model, Am. J. Neurodegener. Dis., 6, 15
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Sorted by citations
Items 101–131 of 131
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Gupta, S., Polit, L. D., Fitzgerald, M., Rowland, H. A., Murali, D., Buckley, N. J., & Subramaniam, S. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1139287 · Cited by 3
Lee, H., Aylward, A. J., Pearse, R. V., Hsieh, Y., Augur, Z. M., Benoit, C. R., Chou, V., Knupp, A., Pan, C., Goberdhan, S., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.02.25.530017 · Cited by 4
Self-citationNguyen, L. D., Wei, Z., Silva, M. C., Barberán-Soler, S., Rabinovsky, R., Muratore, C., Stricker, J. M. S., Hortman, C., Young‐Pearse, T. L., Haggarty, S. J., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.11.01.514550 · Cited by 3
Self-citationOlson, M. N., Dawes, P., Murray, L. F., Barton, N., Sundstrom, J., Orszulak, A. R., Chigas, S. M., Tran, K., Aylward, A. J., Caliandro, M. F., et al. (2026) · npj Dementia · doi:10.1038/s44400-026-00066-y · Cited by 7
Mapping key mitochondrial genes in Alzheimer’s disease through human tissue and iPSC derived neurons
Dong, D., Ahmed, W., Sagar, R., Boyd, R. J., & Mahairaki, V. (2025) · Scientific Reports · doi:10.1038/s41598-025-27019-4 · Cited by 3
Amyloid beta binding partners in the brain tissue of older adults
Oveisgharan, S., Yu, L., Wang, Y., Yang, J., Vialle, R. A., Lopes, K. D. P., Tasaki, S., Young‐Pearse, T. L., Jager, P. L. D., Petyuk, V., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70882 · Cited by 2
Self-citationAugur, Z. M., Fogo, G. M., Arbery, M. R., Stern, A. M., Benoit, C. R., Hsieh, Y., & Young‐Pearse, T. L. (2025) · Acta Neuropathologica Communications · doi:10.1186/s40478-025-02103-y · Cited by 5
“OPTN iPSCs were differentiated into neurons (iNs) using NGN2 overexpression, as previously described [24, 76].”
InfluentialSelf-citationClark, K. A., White, A. J., Pasławski, W., Alexander, K. D., Peng, S., Young‐Pearse, T. L., Svenningsson, P., Selkoe, D. J., & Ho, G. P. H. (2025) · Molecular Biology of the Cell · doi:10.1091/mbc.e24-08-0376 · Cited by 2
“2). iNs BR33, a normal control from an individual with no evidence of neurodegenerative disease, has been described (Lagomarsino et al. , 2021) and was used in Figures 1, 2 and 4, and Supplemental Figure S1.”
Self-citationTranslating Alzheimer’s disease proteomics into drug discovery opportunities
Drummond, E., Werry, E. L., Kavanagh, T., Genoud, S., Cho, A., Chen, S., Du, J., Hibbs, D. E., & Kassiou, M. (2026) · Molecular Neurodegeneration Advances · doi:10.1186/s44477-026-00035-y · Cited by 2
“…correlate with Aβ plaque burden and cognitive impairment for individual patient donors, evidencing the ability of these cells to accurately replicate patient-level AD features in culture [129]. iPSC-derived cells can also be manipulated to induce phenotypic features of AD absent at baseline.”
Investigating the Causal Links between the Aging Process and Alzheimer’s Disease Pathogenesis
Seok, J.-H., Lee, H., & Seo, J. (2026) · International Journal of Stem Cells · doi:10.15283/ijsc25100 · Cited by 1
“Consequently, whereas iNEUs derived from patients can re-capitulate certain genetic aspects of a disease (96-98), the absence of a crucial aging context means that these phenotypes are often restricted to the earliest manifestations of the pathology, reflecting an asymptomatic or prodromal stage…”
Self-citationSaunders, D. M., Kearns, N. A., Ng, B., Sultan, F. A., Vyas, H., Vialle, R. A., Clark, E. M., Tissera, S. L. D., Xu, J., Bennett, D. A. A., et al. (2026) · Stem Cell Research · doi:10.1016/j.scr.2026.104017 · Cited by 1
Self-citationHighly toxic Aβ begets more Aβ
Kemeh, M. M., & Lazo, N. D. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.390983 · Cited by 1
Tam, R. W., & Keung, A. J. (2023) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2023.103876 · Cited by 1
Predictive Network Analysis Identifies JMJD6 and Other Novel Key Drivers in Alzheimer’s DiseasePreprint
Merchant, J. P., Zhu, K., Henrion, M., Zaidi, S. A. J., Branden, L., Moein, S., Alamprese, M., Pearse, R., Bennett, D. A., Ertekin-Taner, N., et al. (2022) · bioRxiv · doi:10.1101/2022.10.19.512949 · Cited by 1
“We used shRNA-mediated knockdown in human iPSCderived neurons (iNs)[55-57] and measured levels of Aβ38, Aβ40, and Aβ42 as well as tau and p231-tau.”
BackgroundMethodSelf-citationHudgins, A. D., Zhou, S.-W., Arey, R. N., Murphy, C., & Suh, Y. (2022) · bioRxiv · doi:10.1101/2022.08.19.504537 · Cited by 1
Lomoio, S., Pandey, R. S., Rouleau, N., Menicacci, B., Kim, W., Cantley, W. L., Haydon, P., Bennett, D. A., Young-Pearse, T. L., Carter, G., et al. (2022) · bioRxiv · doi:10.1101/2022.07.21.501004 · Cited by 1
Self-citationFrazel, P., Labib, D., Fisher, T., Brosh, R., Pirianian, N., Marchildon, A., Boeke, J., Fossati, V., & Liddelow, S. (2021) · bioRxiv · doi:10.1101/2021.12.07.471509 · Cited by 1
Modeling human neurodegeneration with iPSCs: opportunities, limitations, and the challenge of aging
Wang, S., Elia, L., Liu, W., & Finkbeiner, S. M. (2026) · Journal of Clinical Investigation · doi:10.1172/jci209602
“High-penetrance mutations reveal convergent and disease-specific phenotypes . iPSC-derived models have successfully recapitulated multiple hallmark features of NDDs (19, 24, 25).”
Augur, Z. M., Fogo, G. M., Benoit, C. R., Kearney, M., Terzioğlu, G., Murphy, Z. R., Arbery, M. R., Comandante-Lou, N., Duong, D. M., Seyfried, N. T., et al. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2528514123 · Cited by 3
Self-citationTowards Improved P2X7R Cellular Models for Alzheimer’s Disease Drug Discovery
Agius, C. T. A., McKenzie, A. D. J., Woollett, K., Werry, E. L., & Kassiou, M. (2026) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.6c00089
Palollathil, A., Najar, M. A., Pervaje, R., Raju, R., Prasad, T. S. K., & Modi, P. K. (2026) · Neurochemistry International · doi:10.1016/j.neuint.2026.106268
Chintalapally, S., Rajanala, K., & Upadhyay, A. (2026) · Frontiers in Neuroscience · doi:10.3389/fnins.2026.1912268
Fisher, T. M., Limone, F., Smith, M. D., Wright, C., Kukanja, P., Lu, P., Limberg, K. C., Pirjanian, N., Zulueta, J., Fossati, V., et al. (2026) · Cell Reports · doi:10.64898/2026.07.29.741554 · Cited by 1
Guruacharya, A., Härtung, T., dos Reis, R. S., Moreira, N. C. D. S., Attisano, L., Bolognin, S., Iqbal, K., & Rajbanshi, B. (2026) · Stem Cell Reports · doi:10.1016/j.stemcr.2026.103051
Mamais, A., Batchelor, R. D., Aravindraja, C., Ladd, T. B., Shute, A. J., Subrahmanian, N., Maio, N., Vulpe, C. D., & LaVoie, M. J. (2026) · Molecular Neurodegeneration · doi:10.1186/s13024-026-00979-5 · Cited by 2
“BR33 were derived from a Caucasian donor, who was deeply phenotyped as part of the ROS/MAP longitudinal aging studies [53, 54] and determined to not be cognitively impaired at death at age > 89 and free from genetic variants that confer risk of PD. ND35371 (R1441C heterozygous) and ND50051 (G2019S…”
Rizzo, S. J. S. (2025) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2025.103138
“…can also be preserved by direct conversion to neurons and astrocytes even from skin biopsies derived first into fibroblast lines or from peripheral blood mononuclear cells (PBMCs), which have been shown to be an excellent surrogate for brain at the transcriptome and proteome levels [13,15,16].”
Towards the establishment of treatments for neurodegenerative diseases using human iPSCs
Inoue, H. (2025) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2025.103132
Buckley, N., & Rowland, H. (2025) · Stem Cells · doi:10.1093/stmcls/sxaf031
“19 These studies are important for 2 principle reasons.”
Hudgins, A. D., Zhou, S., Arey, R. N., Rosenfeld, M. G., Murphy, C. T., & Suh, Y. (2024) · Neuron · doi:10.1016/j.neuron.2024.04.009 · Cited by 4
iPSC-Astrocyte morphology reflects patient clinical markersPreprint
Rowland, H. A., Miller, G., Liu, Q., Sharp, N. R., Ng, B., Wei, T., Arunasalam, K., Koychev, I., Hedegaard, A., Ribe, E. M., et al. (2023) · bioRxiv · doi:10.1101/2023.07.15.548687
“However, recent studies have demonstrated that clinical markers are indeed reflected by iPSC-derived neurons from individuals with sAD, including secreted β-amyloid (Aβ) levels and synaptic vulnerability [3, 4].”
BackgroundNeurons from individual early Alzheimer’s disease patients reflect their clinical vulnerability
Ng, B., Rowland, H., Wei, T., Arunasalam, K., Hayes, E. M., Koychev, I., Hedegaard, A., Ribe, E. M., Chan, D., Chessell, T., et al. (2021) · bioRxiv · doi:10.1101/2021.11.09.467891
Metadata
- Authors
- Lagomarsino, V. N., Pearse, R. V., Liu, L., Hsieh, Y.-C., Fernandez, M. A., Vinton, E. A., Paull, D., Felsky, D., Tasaki, S., Gaiteri, C., Vardarajan, B., Lee, H., Muratore, C. R., Benoit, C. R., Chou, V., Fancher, S. B., He, A., Merchant, J. P., Duong, D. M., Martinez, H., Zhou, M., Bah, F., Vicent, M. A., Stricker, J. M. S., Xu, J., Dammer, E. B., Levey, A. I., Chibnik, L. B., Menon, V., Seyfried, N. T., De Jager, P. L., Noggle, S., Selkoe, D. J., Bennett, D. A., & Young-Pearse, T. L.
- Affiliations
- Brigham and Women's Hospital (US)
- New York Stem Cell Foundation (US)
- Centre for Addiction and Mental Health (CA)
- Rush University Medical Center (US)
- Columbia University Irving Medical Center (US)
- Emory University (US)
- Harvard University (US)
- ORCID
- Lagomarsino, Valentina N.
- Pearse, Richard V.
- Liu, Lei
- Hsieh, Yi-Chen
- Fernandez, Marty A.
- Vinton, Elizabeth A.
- Paull, Daniel
- Felsky, Daniel
- Tasaki, Shinya
- Gaiteri, Chris
- Vardarajan, Badri
- Lee, Hyo
- Benoit, Courtney R.
- Chou, Vicky
- Merchant, Julie P.
- Duong, Duc M.
- Stricker, Jonathan M.S.
- Xu, Jishu
- Dammer, Eric B.
- Levey, Allan I.
- Chibnik, Lori B.
- Menon, Vilas
- Seyfried, Nicholas T.
- Noggle, Scott
- Selkoe, Dennis J.
- Bennett, David A.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2021-11
- Volume
- 109
- Issue
- 21
- Pages
- 3402-3420.e9
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC8571042
- OpenAlex
- W3198364341
- Cited by
- 151
- References
- 73
- Citations by year
- 2026: 15 · 2025: 37 · 2024: 36 · 2023: 37 · 2022: 20 · 2021: 6
- FWCI
- 16.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 367 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R21MH118576, R01AG055909, RF1AG057440, R01AG061798, U01AG046170, R21AG056011, U01AG061356, R01NS117446, R01AG061894)
- National Institute on Aging (R01AG30146, R01AG36836, U01AG32984, U01AG46152, R01AG15819, R01AG017917, P30AG10161)
- New York Stem Cell Foundation
- Lawrence Ellison Foundation
- Illinois Department of Public Health
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, iPSC-derived neurons, genetic risk, amyloid-beta, tau protein, amyloid plaques, neurofibrillary tangles, cognitive decline, neuropathology, proteomic profiling, RNA profiling, protein networks, brain tissue
- MeSH terms
- Aged, Alzheimer Disease, Cognition, Humans, Neurons, Amyloid beta-Peptides, tau Proteins, Proteomics, Induced Pluripotent Stem Cells
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