ArticleNeuron2021
Stem cell-derived neurons reflect features of protein networks, neuropathology, and cognitive outcome of their aged human donors.
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Article in Neuron, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 1 of them a synthesis that pooled it.
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102citing papers in PubMed, 1 pooled it
17.8field-weighted citation impact, top 1% of its field
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Who cites it
102 citing papers in PubMed, 1 synthesis or guideline pooled it, 171 citations in OpenAlex.
- Investigation of the independent role of a rare APOE variant (L28P; APOE*4Pittsburgh) in late-onset Alzheimer disease.Neurobiology of aging · 2023Pooled it
- Modeling human neurodegeneration with iPSCs: opportunities, limitations, and the challenge of aging.The Journal of clinical investigation · 2026Review
- Brain organoids in Alzheimer disease and related tauopathies: Challenges and opportunities for translational readiness.Stem cell reports · 2026Review
- Modeling stimulus-induced stress responses in microglia-like cells using a commercial iPSC-dCas9-KRAB line.Stem cell research · 2026Article
- Investigating the Causal Links between the Aging Process and Alzheimer's Disease Pathogenesis.International journal of stem cells · 2026Review
- PSEN1 mutant marmoset fibroblasts mimic multi-omic signatures of Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- Brain Endothelial Soluble ST2 Production and Cerebral Edema in a Rat Model of Ischemic Stroke.Annals of neurology · 2026Article
- Unbiased data-driven analysis of five amyloid-beta peptides for biomarker investigations in familial Alzheimer's disease.Brain communications · 2026Article
- A high-throughput, quantitative platform using 2D dissociated human cerebral organoids to model neuroinflammation in Alzheimer's disease.NPJ dementia · 2026Article
- Retinoic acid-related orphan receptor alpha (RORα) as a candidate multi-pathway target in Alzheimer's disease: mechanisms and therapeutic prospects.Frontiers in neuroscience · 2026Review
- POU3F2 regulates canonical Wnt signalling via SOX13 and ADNP to expand the neural progenitor population.Brain : a journal of neurology · 2025Article
- Recent advances in model systems for interrogating diseases of brain aging and associated dementia: Toward human-relevant endophenotypes.Current opinion in neurobiology · 2025Review
- Mapping key mitochondrial genes in Alzheimer's disease through human tissue and iPSC derived neurons.Scientific reports · 2025Article
- Tau seeding in neurons enabled by transient endolysosomal perforations are confined within endolysosomes.bioRxiv : the preprint server for biology · 2025Article
- Integrative brain omics approach highlights sn-1 lysophosphatidylethanolamine in Alzheimer's dementia.Nature communications · 2025Article
- INPP5D/SHIP1 is a dual regulator of endo-lysosome function and selective phagocytosis in human microglia.bioRxiv : the preprint server for biology · 2025Article
- Genetic and proteomic analysis identifies BAG3 as an amyloid-responsive regulator of neuronal proteostasis.Acta neuropathologica · 2025Article
- Induced Pluripotent Stem Cells Derived Cellular Models for Investigating Parkinson's Disease Pathogenesis and Drug Screening.Stem cell reviews and reports · 2025Review
- Alzheimer's disease patient brain extracts induce multiple pathologies in novel vascularized neuroimmune organoids for disease modeling and drug discovery.Molecular psychiatry · 2025Article
- Article
42 more citing papers are in PubMed but not listed here.
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Authors and funding
35 authors at 7 institutions in 2 countries.
Valentina N LagomarsinoAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Richard V PearseAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Lei LiuAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Yi-Chen HsiehAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Marty A FernandezAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Elizabeth A VintonAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Daniel PaullNew York Stem Cell Foundation Research Institute, New York, NY, USA.
Daniel FelskyKrembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry and Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
Shinya TasakiRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Chris GaiteriRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Badri VardarajanCenter for Translational and Computational Neuroimmunology, Department of Neurology and the Taub Institute for the Study of Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, NY, USA.
Hyo LeeAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Christina R MuratoreAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Courtney R BenoitAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Vicky ChouAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Seeley B FancherAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Amy HeAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Julie P MerchantAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Duc M DuongDepartment of Biochemistry, Emory School of Medicine, Atlanta, GA, USA.
Hector MartinezNew York Stem Cell Foundation Research Institute, New York, NY, USA.
Monica ZhouNew York Stem Cell Foundation Research Institute, New York, NY, USA.
Fatmata BahAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Maria A VicentAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Jonathan M S StrickerAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Jishu XuRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Eric B DammerDepartment of Biochemistry, Emory School of Medicine, Atlanta, GA, USA.
Allan I LeveyDepartment of Neurology, Emory School of Medicine, Atlanta, GA, USA.
Lori B ChibnikDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Vilas MenonCenter for Translational and Computational Neuroimmunology, Department of Neurology and the Taub Institute for the Study of Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, NY, USA.
Nicholas T SeyfriedDepartment of Biochemistry, Emory School of Medicine, Atlanta, GA, USA; Department of Neurology, Emory School of Medicine, Atlanta, GA, USA.
Philip L De JagerCenter for Translational and Computational Neuroimmunology, Department of Neurology and the Taub Institute for the Study of Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, NY, USA.
Scott NoggleNew York Stem Cell Foundation Research Institute, New York, NY, USA.
Dennis J SelkoeAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Tracy L Young-PearseAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA. Electronic address: tpearse@bwh.harvard.edu.
Harvard University · USBrigham and Women's Hospital · USEmory University · USNew York Stem Cell Foundation · USRush University Medical Center · USColumbia University · USCentre for Addiction and Mental Health · CA
Funding
Alzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4MTRANSGENICS AND PRESENILIN FUNCTIONP01AG015379 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI TANZI, RUDOLPH EMILE · 1998 to 2023
$51.3MMedical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0MSUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI LEURGANS, SUE E. · 1991 to 2020
$49.1MEPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3MIntegrative Network Biology Approaches to Identify, Characterize and Validate Molecular Subtypes in Alzheimer's DiseaseU01AG046170 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI WANG, MINGHUI, ZHANG, BIN · 2013 to 2022
$26.0MRISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4MMulti-omic network-directed proteoform discovery, dissection and functional validation to prioritize novel AD therapeutic targetsU01AG061356 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2018 to 2022
$13.7MPathway discovery, validation and compound identification for Alzheimer's disease - SupplementU01AG046152 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2013 to 2017
$13.6MAlzheimer variants: Propagation of shared functional changes across cellular networksU01AG072572 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI DE JAGER, PHILIP L, ST GEORGE-HYSLOP, PETER HENRY · 2021 to 2025
$8.5MGenetic Epidemiology of Cognitive Decline in an Aging Population SampleR01AG030146 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI EVANS, DENIS A · 2007 to 2018
$6.2MProbing Heterogeneity of Alzheimer's Disease Using iPSCsR01AG055909 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI Tracy L YOUNG-PEARSE · 2018 to 2026
$5.7MNIA NIH HHS P01 AG015379NIA NIH HHS P30 AG010161NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG030146NIA NIH HHS R01 AG036836NIA NIH HHS R01 AG055909NIA NIH HHS R01 AG061798NIA NIH HHS R01 AG061894NIA NIH HHS R21 AG056011NIA NIH HHS RF1 AG057440NIA NIH HHS RF1 AG057457NIA NIH HHS RF1 AG057473NIA NIH HHS U01 AG032984NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG046170NIA NIH HHS U01 AG061356NIA NIH HHS U01 AG072572NIGMS NIH HHS T32 GM007753NIMH NIH HHS R21 MH118576NINDS NIH HHS R01 NS117446NINDS NIH HHS RF1 NS117446
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.
Indexed as
Alzheimer DiseaseInduced Pluripotent Stem CellsAgedAmyloid beta-PeptidesCognitionHumansNeuronsProteomicstau ProteinsAmyloid beta-Peptidestau ProteinsAlzheimer’sAβgeneticsiPSCLOADMAPTneuronPP1PRStau
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