ArticleCell2024
Cross-disorder and disease-specific pathways in dementia revealed by single-cell genomics.
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Article in Cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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38citing papers in PubMed, 1 pooled it
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Association between different sodium-glucose co-transporter 2 inhibitors and the risk of dementia: a network meta-analysis.Frontiers in endocrinology · 2026Pooled it
- Single-nucleus transcriptomics reveals cell type-specific remodeling and epilepsy-associated microglia.iScience · 2026Article
- Integrative analysis of single-cell multi-omics reveals heterogeneity in piriform cortex principal neurons and their selective vulnerability in Alzheimer's disease.Clinical and translational medicine · 2026Article
- Single-cell transcriptomics of human brain disorders.Molecular psychiatry · 2026Review
- 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
- Article
- The deficiency of KIF2C leads to abnormal distribution of cortical neurons and behavioral deficits in mice.iScience · 2026Article
- Neurodegenerative diseases and immune system: From pathogenic mechanism to therapy.Neural regeneration research · 2026Article
- Single-cell transcriptomic atlas of frontoinsular cortex reveals molecular correlates of selective neuronal vulnerability in FTD.bioRxiv : the preprint server for biology · 2026Article
- Cerebrovascular Single-Nucleus RNA-Seq Reveals Heat Shock Activation and Vascular Remodeling in Alzheimer's Disease and Primary Tauopathies.Research square · 2026Article
- Kat5 cKO mouse replicates biological domain signatures associated with Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Emerging directions in tauopathy research.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Single-nucleus epigenomic dysregulation unmasks genetic risk-associated neurodegenerative glia states.Nature communications · 2026Article
- Integrative genomic and functional analyses reveal NINL as a modulator of tau aggregation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Identifying Adaptive Footprints in the Presence of Demographic Uncertainty.Genome biology and evolution · 2026Article
- A critical appraisal of the link between apolipoprotein E and Tau.Current opinion in neurology · 2026Review
- Decoding neurodegeneration one cell at a time.The Journal of clinical investigation · 2026Review
- Single-Nucleus Transcriptomics Reveals Cell Type-Specific Remodeling and Epilepsy-Associated Microglia.bioRxiv : the preprint server for biology · 2026Article
- Article
- Integrative epigenomic landscape of Alzheimer's Disease brains reveals oligodendrocyte molecular perturbations associated with tau.Nature communications · 2026Article
Corrections and comments
- Update of
Authors and funding
25 authors.
Jessica E RexachProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: jrexach@mednet.ucla.edu.
Yuyan ChengProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Lawrence ChenProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Damon PolioudakisProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Li-Chun LinDepartment of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA.
Vivianne MitriProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Andrew ElkinsProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Xia HanProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Mai YamakawaProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Anna YinProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Daniela CaliniNeuroscience and Rare Diseases, Roche Pharma Research and Early Development, F. Hoffman-LaRoche Ltd., Basel, Switzerland.
Riki KawaguchiProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jing OuProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jerry HuangProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Christopher WilliamsProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
John RobinsonDepartment of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Stephanie E GausDepartment of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA.
Salvatore SpinaDepartment of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA.
Edward B LeeDepartment of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Lea T GrinbergDepartment of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA, USA.
Harry VintersProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
John Q TrojanowskiDepartment of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
William W SeeleyDepartment of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA, USA.
Dheeraj MalhotraNeuroscience and Rare Diseases, Roche Pharma Research and Early Development, F. Hoffman-LaRoche Ltd., Basel, Switzerland.
Daniel H GeschwindProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute of Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: dhg@mednet.ucla.edu.
Funding
TDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2MPrPSc SPECIFIC INTERACTION WITH NOVEL PrP-Fc FUSION PROTEINSP50AG023501 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HUANG, YADONG · 2004 to 2018
$27.1MResearch Education ComponentP30AG072979 · NIA · UNIVERSITY OF PENNSYLVANIA · PI DAVID A WOLK · 2021 to 2026
$24.8MUnderstanding Environmental Contributions to Heterogeneity in bvFTD.P01AG066597 · NIA · UNIVERSITY OF PENNSYLVANIA · PI David John Irwin, Corey T McMillan · 2020 to 2026
$18.8MProject IV "Tackling Heterogeneity of Cognitive Trajectory in LBD"U19AG062418 · NIA · UNIVERSITY OF PENNSYLVANIA · PI CHEN-PLOTKIN, ALICE S · 2019 to 2023
$18.1MInvestigating regional and cellular vulnerabilities to tau pathology in young-onset Alzheimer's diseaseR01AG075802 · NIA · MAYO CLINIC JACKSONVILLE · PI BERNARDINO Francesco GHETTI, Lea Tenenholz Grinberg · 2022 to 2026
$15.5MClinical Features and Neuropathological Basis of Sleep Wake Behavior in Alzheimer's and PSPR01AG060477 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Lea Tenenholz Grinberg, Thomas C Neylan · 2019 to 2026
$8.2MImpact of coding and non-coding variation in progressive supranuclear palsyUG3NS104095 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DICKSON, DENNIS WILLIAM, GESCHWIND, DANIEL H · 2017 to 2019
$3.6MNeuropathological changes underlying clinical heterogeneity in Alzheimer diseaseK24AG053435 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRINBERG, LEA TENENHOLZ · 2016 to 2025
$1.8MSingle cell and tissue level functional genomic analysis of astrocyte-related mechanisms in tauopathyK08NS105916 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REXACH, JESSICA E · 2019 to 2023
$1.1MNIA NIH HHS K24 AG053435NIA NIH HHS P01 AG019724NIA NIH HHS P01 AG066597NIA NIH HHS P30 AG072979NIA NIH HHS P50 AG023501NIA NIH HHS R01 AG060477NIA NIH HHS R01 AG075802NIA NIH HHS U19 AG062418NINDS NIH HHS K08 NS105916NINDS NIH HHS UG3 NS104095
Abstract
The development of successful therapeutics for dementias requires an understanding of their shared and distinct molecular features in the human brain. We performed single-nuclear RNA-seq and ATAC-seq in Alzheimer's disease (AD), frontotemporal dementia (FTD), and progressive supranuclear palsy (PSP), analyzing 41 participants and ∼1 million cells (RNA + ATAC) from three brain regions varying in vulnerability and pathological burden. We identify 32 shared, disease-associated cell types and 14 that are disease specific. Disease-specific cell states represent glial-immune mechanisms and selective neuronal vulnerability impacting layer 5 intratelencephalic neurons in AD, layer 2/3 intratelencephalic neurons in FTD, and layer 5/6 near-projection neurons in PSP. We identify disease-associated gene regulatory networks and cells impacted by causal genetic risk, which differ by disorder. These data illustrate the heterogeneous spectrum of glial and neuronal compositional and gene expression alterations in different dementias and identify therapeutic targets by revealing shared and disease-specific cell states.
Indexed as
Alzheimer DiseaseFrontotemporal DementiaGene Regulatory NetworksGenomicsNeuronsSingle-Cell AnalysisSupranuclear Palsy, ProgressiveAgedAged, 80 and overBrainDementiaFemaleHumansMaleMiddle AgedNeurogliadrug discoveryfunctional genomicsKCNH7MAFGmulti-omicsNFE2L1NLGN1OPCMLPDE1Ctauopathy
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.