Cited by 151Alzheimer's disease research and treatmentsPluripotent Stem Cells ResearchDementia and Cognitive Impairment Research

Stem cell-derived neurons reflect features of protein networks, neuropathology, and cognitive outcome of their aged human donors

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Lagomarsino, Valentina N., Pearse, Richard V., Liu, Lei, Hsieh, Yi-Chen, Fernandez, Marty A., Vinton, Elizabeth A., Paull, Daniel, Felsky, Daniel +27 more·2021·Neuron

Abstract

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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Crossref · 10.1016/j.neuron.2021.08.003

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  • We detected several SHIP1 binding partners previously identified in other myeloid cells, such as SH3KBP1, GRB2, SHC1, DOK2, ARAP1, CD2AP.

    “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]

    Citation 21 is attached specifically to CD2AP. The cited paper’s Results discuss protein networks in stem-cell-derived neurons and Alzheimer’s disease, but the passages available from our copy do not address CD2AP as a SHIP1 binding partner in myeloid cells. Searches for CD2AP, SHIP1/INPP5D, and the other named partners found no supporting passage; page numbers were not provided. (LLM, conf=0.76)

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  1. GARCIA-ESPARCIA P, SIDERIS-LAMPRETSAS G, HERNANDEZ-ORTEGA K, GRAU-RIVERA O, SKLAVIADIS T, GELPI E & FERRER I 2017. Altered mechanisms of protein synthesis in frontal cortex in Alzheimer disease and a mouse model. Am J Neurodegener Dis, 6, 15– 25. 28695061 PMC5498849
  2. ODDO S, BILLINGS L, KESSLAK JP, CRIBBS DH & LAFERLA FM 2004. Abeta immunotherapy leads to clearance of early, but not late, hyperphosphorylated tau aggregates via the proteasome. Neuron, 43, 321– 32. 15294141
  3. PAULL D, SEVILLA A, ZHOU H, HAHN AK, KIM H, NAPOLITANO C, TSANKOV A, SHANG L, KRUMHOLZ K, JAGADEESAN P, WOODARD CM, SUN B, VILBOUX T, ZIMMER M, FORERO E, MOROZIEWICZ DN, MARTINEZ H, MALICDAN MC, WEISS KA, VENSAND LB, DUSENBERRY CR, POLUS H, SY KT, KAHLER DJ, GAHL WA, SOLOMON SL, CHANG S, MEISSNER A, EGGAN K & NOGGLE SA Automated, high-throughput derivation, characterization and differentiation of induced pluripotent stem cells. Nat Methods. PMC13012702 26237226

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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)
Venue
Neuron
Publisher
Elsevier BV
Published
2021-11
Volume
109
Issue
21
Pages
3402-3420.e9
ISSN
0896-6273 (ISSN-L)
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
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
  • Health Sciences › Medicine › Physiology › 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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