ArticleCell2023
Single-cell atlas reveals correlates of high cognitive function, dementia, and resilience to Alzheimer's disease pathology.
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Article in Cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 369 papers, 3 of them syntheses that pooled it.
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369citing papers in PubMed, 3 pooled it
67.6field-weighted citation impact, top 1% of its field
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Who cites it
369 citing papers in PubMed, 3 syntheses or guidelines pooled it, 441 citations in OpenAlex.
- A meta-analysis of single-nucleus expression quantitative trait loci linking genetic risk to brain disorders.Nature genetics · 2026Pooled it
- Matching heterogeneous cohorts by projected principal components reveals two novel Alzheimer's disease-associated genes in the Hispanic population.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Pooled it
- Improving reproducibility of differentially expressed genes in single-cell transcriptomic studies of neurodegenerative diseases through meta-analysis.Nature communications · 2025Pooled it
- Design, synthesis and biological evaluation of donepezil-safinamide hybrids as dual AChE and MAO-B inhibitor for Alzheimer's disease treatment.Journal of enzyme inhibition and medicinal chemistry · 2026Article
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- Why are some neurons spared in neurodegeneration? Cellular subtype identity maintenance as a candidate threshold-setting mechanism.PLoS biology · 2026Article
- Convergent mitochondrial impairment and apoptosis driven by simultaneous down-regulation of multiple genes at 11p11.2 in Alzheimer's disease.Molecular psychiatry · 2026Article
- Personalized single-cell transcriptomics reveals molecular diversity in Alzheimer's disease.Nature communications · 2026Article
- Efficient differential expression analysis of large-scale single-cell transcriptomics data using Dreamlet.Nature communications · 2026Article
- AI-based characterization of Alzheimer's disease phenotypes from population-scale single-cell data.Nature medicine · 2026Article
- Distinct cellular phenotypes of language and executive decline in amyotrophic lateral sclerosis.Cell · 2026Article
- Transcriptome changes of disinhibited somatostatin neurons in the medial prefrontal cortex mediating male-specific stress resilience.Research square · 2026Article
- Genome-wide association analyses highlight the neuronal contribution to multiple sclerosis susceptibility.Nature genetics · 2026Article
- Article
- Single-cell transcriptomics of human brain disorders.Molecular psychiatry · 2026Review
- Reduced expression of Brain Expressed X-linked genes in Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2026Article
- A microprotein atlas of the human frontal cortex in Alzheimer's disease.Nature aging · 2026Article
- DeOPUS: cellular deconvolution via optimized power-transformed unmixing with shrinkage.Briefings in bioinformatics · 2026Article
- Hippocampal snRNA-seq in Collaborative Cross reveals molecular signatures of cognitive resilience independent of chronological aging.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
309 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
30 authors at 3 institutions in 1 country.
Hansruedi MathysPicower Institute for Learning and Memory, MIT, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA; University of Pittsburgh Brain Institute and Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. Electronic address: mathysh@pitt.edu.
Zhuyu PengPicower Institute for Learning and Memory, MIT, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA.
Carles A BoixComputer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Matheus B VictorPicower Institute for Learning and Memory, MIT, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA.
Noelle LearyPicower Institute for Learning and Memory, MIT, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA.
Sudhagar BabuUniversity of Pittsburgh Brain Institute and Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Ghada AbdelhadyUniversity of Pittsburgh Brain Institute and Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Xueqiao JiangPicower Institute for Learning and Memory, MIT, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA.
Ayesha P NgPicower Institute for Learning and Memory, MIT, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA.
Kimia GhafariUniversity of Pittsburgh Brain Institute and Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Alexander K KuniskyUniversity of Pittsburgh Brain Institute and Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Julio ManteroComputer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Kyriaki GalaniComputer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Vanshika N LohiaUniversity of Pittsburgh Brain Institute and Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Gabrielle E FortierUniversity of Pittsburgh Brain Institute and Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Yasmine LotfiUniversity of Pittsburgh Brain Institute and Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Jason IveyUniversity of Pittsburgh Brain Institute and Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Hannah P BrownUniversity of Pittsburgh Brain Institute and Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Pratham R PatelUniversity of Pittsburgh Brain Institute and Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Nehal ChakrabortyUniversity of Pittsburgh Brain Institute and Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Jacob I BeaudwayUniversity of Pittsburgh Brain Institute and Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Elizabeth J ImhoffUniversity of Pittsburgh Brain Institute and Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Cameron F KeelerUniversity of Pittsburgh Brain Institute and Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Maren M McChesneyUniversity of Pittsburgh Brain Institute and Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Haishal H PatelUniversity of Pittsburgh Brain Institute and Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Sahil P PatelUniversity of Pittsburgh Brain Institute and Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Megan T ThaiUniversity of Pittsburgh Brain Institute and Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
David A BennettRush Alzheimer's Disease Center, Chicago, IL 60612, USA.
Manolis KellisComputer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: manoli@mit.edu.
Li-Huei TsaiPicower Institute for Learning and Memory, MIT, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: lhtsai@mit.edu.
University of Pittsburgh · USBroad Institute · USRush University · US
Funding
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1MEPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3MRush Alzheimer's Disease Research CenterP30AG072975 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI Lisa L Barnes, Julie A. Schneider · 2021 to 2026
$24.7MRISK 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
$13.6MSingle Cell Transcriptomic and Epigenomic Dissection of Opioid and Cocaine Responses in HIVU01DA053631 · NIDA · BROAD INSTITUTE, INC. · PI HEIMAN, MYRIAM, KELLIS, MANOLIS · 2021 to 2025
$12.6MMapping the vulnerable locus coeruleus pathways in aging and ADU01AG077227 · NIA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Kwanghun Chung, Li-Huei Tsai · 2022 to 2026
$9.6MIdentification of TDP-43 Modifiers Through Single-Cell Transcriptional and Epigenomic Dissection of ALS and FTLD-MNDR01NS127187 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BELZIL, VERONIQUE, DONNELLY, CHRISTOPHER JAMES · 2021 to 2025
$9.1MPredoctorial Training in Basic NeuroscienceT32NS007433 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MERINEY, STEPHEN D · 1998 to 2022
$8.0MEpigenomic, transcriptional and cellular dissection of Alzheimer's variantsR01AG058002 · NIA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI HYMAN, BRADLEY T., JAENISCH, RUDOLF · 2017 to 2021
$7.9MElucidating the Molecular Mechanisms of Neuropsychiatric Symptoms in Alzheimer's DiseaseR01AG062335 · NIA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI KELLIS, MANOLIS, TSAI, LI-HUEI · 2018 to 2022
$6.5MHoward Hughes Medical InstituteNHGRI NIH HHS R01 HG008155NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG072975NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG058002NIA NIH HHS R01 AG062335NIA NIH HHS R01 AG067151NIA NIH HHS R01 AG074003NIA NIH HHS R01 AG081017NIA NIH HHS RF1 AG054012NIA NIH HHS RF1 AG054321NIA NIH HHS RF1 AG062377NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG061356NIA NIH HHS U01 AG077227NIDA NIH HHS U01 DA053631NIGMS NIH HHS T32 GM087237NIMH NIH HHS U01 MH119509NINDS NIH HHS R01 NS127187NINDS NIH HHS RF1 NS129032NINDS NIH HHS T32 NS007433NINDS NIH HHS U01 NS110453NINDS NIH HHS UG3 NS115064NINDS NIH HHS UH3 NS115064
Abstract
Alzheimer's disease (AD) is the most common cause of dementia worldwide, but the molecular and cellular mechanisms underlying cognitive impairment remain poorly understood. To address this, we generated a single-cell transcriptomic atlas of the aged human prefrontal cortex covering 2.3 million cells from postmortem human brain samples of 427 individuals with varying degrees of AD pathology and cognitive impairment. Our analyses identified AD-pathology-associated alterations shared between excitatory neuron subtypes, revealed a coordinated increase of the cohesin complex and DNA damage response factors in excitatory neurons and in oligodendrocytes, and uncovered genes and pathways associated with high cognitive function, dementia, and resilience to AD pathology. Furthermore, we identified selectively vulnerable somatostatin inhibitory neuron subtypes depleted in AD, discovered two distinct groups of inhibitory neurons that were more abundant in individuals with preserved high cognitive function late in life, and uncovered a link between inhibitory neurons and resilience to AD pathology.
Indexed as
Alzheimer DiseaseBrainAgedCognitionCognitive DysfunctionHumansNeuronsAlzheimer's diseasecognitive impairmentcognitive resiliencecohesin complexDNA damage responseinhibitory neuronsneurodegenerationsingle-cell transcriptomic atlas
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