OSCR

Cell-type signatures of Alzheimer's disease shared across population groups.

Overview

Authors: Tain Luquez1, Jonathan Algoo1, Rebecca Chiu1, Jason A. Mares1, Archana Yadav1, Matti Lam2, Pallavi Gaur1, Xiaoying Lai1, Dylan I. Lee1, Fahad Paryani1, Rafe Batchelor1, Irla Belli1, Jordan Henry1, Bat Hoter-Ishay1, Courteney Mattison1, Lindsey Starr1, Tsering Lama1, Berke Karaahmet1, Wenqing Cao1, Philip L. De Jager1
and 6 other authorsMariko Taga1, Lisa L. Barnes2, David X. Marquez2,3, David A. Bennett2, Ya Zhang1, Vilas Menon1
ORCID iDs: Tain Luquez, Rebecca Chiu, Pallavi Gaur, Dylan I. Lee, Irla Belli, Courteney Mattison, Philip L. De Jager, Ya Zhang, Vilas Menon
  1. Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center,New York, NY USA
  2. Rush Alzheimer’s Disease Center, Rush University Medical Center,Chicago, IL USA
  3. Department of Kinesiology and Nutrition, University of Illinois Chicago,Chicago, IL USA
Institutions: Columbia University Irving Medical Center (United States); Rush University Medical Center (United States); University of Illinois Chicago (United States)
Journal: Nature, volume 657, issue 8130, pages 191-201
Dates: received 19 November 2025; accepted 10 June 2026; published online 15 July 2026; in print 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41586-026-10793-0 · PMID 42457956 · PMCID PMC13538069 · OpenAlex W7168403495
Open access: hybrid, a free copy (OpenAlex)
Status: data only
Categories: genetics / omics (modality), human (organism), Alzheimer's / dementia (population), cellular / molecular (subfield)
Methods: Statistics, Smoothing, state filtering, decompositions, Machine learning, Connectivity
Keywords: Neurodegeneration, Molecular neuroscience, Neuroimmunology
MeSH: Alzheimer Disease*, Astrocytes*, Microglia*, Oligodendroglia*, Black or African American, Brain, Chromatin, Cognitive Dysfunction, Female, Humans, Male, Neurons, Phenotype, Single-Cell Analysis, White People (* major topic)
Topic: Single-cell and spatial transcriptomics (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: U.S. Department of Health and Human Services (R01 AG15819, R01AG17917, U01AG46152, P30-AG10161, P30AG072975, U01AG61356); Rush University (P30AG10161, R01 AG15819); National Institutes of Health (5r01ag017917-20, 3u01ag046152-02s1, 5r01ag015819-21, 5p30ag072975-04, 5u01ag061356-05, 5p30ag010161-12, R01 AG15819, P30AG10161, U01 AG61356, R01AG022018, U01AG46152, R01 AG17917, P30AG072975)
Citations: cited by 2 papers (Europe PMC); 59 references in the paper

Abstract

Genomic studies at single-cell resolution have identified several cell types associated with clinical and pathological traits in Alzheimer’s disease1–9, but have not examined associations that are shared across populations. To bridge this gap, here we use single-nucleus RNA sequencing and assay for transposase-accessible chromatin with sequencing to profile cortical and subcortical regions in post-mortem brain-tissue samples from Latin, white (excluding Latin) and African American (excluding Latin) individuals. Using discrete and continuous dissections of molecular programs, we identify cell-type-specific clusters associated with Alzheimer’s disease in a region-specific manner across all three population groups, including microglial (GPNMB+ and CD74+ subgroups), astrocytic (SERPINH1+, CD44+ and WIF1+ subgroups) and neuronal (SST+ GABAergic and superficial-layer glutamatergic) signatures. We also report continuous gene-expression factors in astrocytes and oligodendrocytes that are not captured by discrete cluster assignments, but which show strong associations with disease phenotypes; these factors are enriched for genes associated with annotated functions such as lipid processing and neurotransmitter reuptake. Finally, we find that molecular programs reveal six distinct subgroups of individuals with cognitive impairment that span all three populations, are not captured by neuropathology, and are instead distinguished by molecular signatures that are not universally present but are nonetheless associated with ante-mortem impairment. Overall, our study identifies key cell types and gene programs implicated in Alzheimer’s disease that are shared across population groups, and underscores how representative sampling can capture both shared signatures and disease heterogeneity, thereby enabling better prioritization of key cell types for further investigation.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none, so it has no map.

Data

Datasets cited

Data availability

All raw data (fastq files) and processed data (post-quality control count tables and cluster identities) are available through the AD Knowledge Portal in Synapse at https://doi.org/10.7303/syn53649093. Batch processing and pooling experimental plan files are available through the AD Knowledge Portal at https://www.synapse.org/Synapse:syn53649030. These files are available by submitting a Data Use Agreement through Synapse, requesting access to AMP AD data. Raw and processed WGS data used for genetic ancestry and polygenic risk scores are available through the AD Knowledge Portal (https://www.synapse.org/Synapse:syn52563603 and referenced in a previous study59. A browsable interface to examine the data is available at https://vmenon.shinyapps.io/ampad2_snrnaseq.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 2, 28 September 2026

  • Publisher: n/a → Nature Portfolio
  • Funding: added U.S. Department of Health and Human Services: R01 AG15819, R01AG17917, U01AG46152, P30-AG10161, P30AG072975, U01AG61356; Rush University: P30AG10161, R01 AG15819; National Institutes of Health: 5r01ag017917-20, 3u01ag046152-02s1, 5r01ag015819-21, 5p30ag072975-04, 5u01ag061356-05, 5p30ag010161-12, R01 AG15819, P30AG10161, U01 AG61356, R01AG022018, U01AG46152, R01 AG17917, P30AG072975

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 26 authors, 3 keywords, 15 MeSH terms, 59 references.

Cite

This paper

Luquez, T., Algoo, J., Chiu, R., Mares, J. A., Yadav, A., Lam, M., Gaur, P., Lai, X., Lee, D. I., Paryani, F., Batchelor, R., Belli, I., Henry, J., Hoter-Ishay, B., Mattison, C., Starr, L., Lama, T., Karaahmet, B., Cao, W., . . . Menon, V. (2026). Cell-type signatures of Alzheimer's disease shared across population groups. Nature, 657(8130), 191-201. https://doi.org/10.1038/s41586-026-10793-0

BibTeX

@article{luquez2026cell,
author = {Luquez, Tain and Algoo, Jonathan and Chiu, Rebecca and Mares, Jason A. and Yadav, Archana and Lam, Matti and Gaur, Pallavi and Lai, Xiaoying and Lee, Dylan I. and Paryani, Fahad and Batchelor, Rafe and Belli, Irla and Henry, Jordan and Hoter-Ishay, Bat and Mattison, Courteney and Starr, Lindsey and Lama, Tsering and Karaahmet, Berke and Cao, Wenqing and De Jager, Philip L. and Taga, Mariko and Barnes, Lisa L. and Marquez, David X. and Bennett, David A. and Zhang, Ya and Menon, Vilas},
title = {{Cell-type signatures of Alzheimer's disease shared across population groups}},
journal = {Nature},
year = {2026},
month = jul,
volume = {657},
number = {8130},
pages = {191--201},
publisher = {Nature Portfolio},
issn = {0028-0836},
doi = {10.1038/s41586-026-10793-0},
url = {https://doi.org/10.1038/s41586-026-10793-0},
pmid = {42457956},
pmcid = {PMC13538069}
}

RIS

TY - JOUR
AU - Luquez, Tain
AU - Algoo, Jonathan
AU - Chiu, Rebecca
AU - Mares, Jason A.
AU - Yadav, Archana
AU - Lam, Matti
AU - Gaur, Pallavi
AU - Lai, Xiaoying
AU - Lee, Dylan I.
AU - Paryani, Fahad
AU - Batchelor, Rafe
AU - Belli, Irla
AU - Henry, Jordan
AU - Hoter-Ishay, Bat
AU - Mattison, Courteney
AU - Starr, Lindsey
AU - Lama, Tsering
AU - Karaahmet, Berke
AU - Cao, Wenqing
AU - De Jager, Philip L.
AU - Taga, Mariko
AU - Barnes, Lisa L.
AU - Marquez, David X.
AU - Bennett, David A.
AU - Zhang, Ya
AU - Menon, Vilas
TI - Cell-type signatures of Alzheimer's disease shared across population groups
T2 - Nature
J2 - Nature
PY - 2026
DA - 2026/07/15
VL - 657
IS - 8130
SP - 191
EP - 201
SN - 0028-0836
PB - Nature Portfolio
DO - 10.1038/s41586-026-10793-0
UR - https://doi.org/10.1038/s41586-026-10793-0
LA - en
ER -

CSL-JSON

{
"id": "10.1038/s41586-026-10793-0",
"type": "article-journal",
"title": "Cell-type signatures of Alzheimer's disease shared across population groups",
"container-title": "Nature",
"author": [
{
"family": "Luquez",
"given": "Tain"
},
{
"family": "Algoo",
"given": "Jonathan"
},
{
"family": "Chiu",
"given": "Rebecca"
},
{
"family": "Mares",
"given": "Jason A."
},
{
"family": "Yadav",
"given": "Archana"
},
{
"family": "Lam",
"given": "Matti"
},
{
"family": "Gaur",
"given": "Pallavi"
},
{
"family": "Lai",
"given": "Xiaoying"
},
{
"family": "Lee",
"given": "Dylan I."
},
{
"family": "Paryani",
"given": "Fahad"
},
{
"family": "Batchelor",
"given": "Rafe"
},
{
"family": "Belli",
"given": "Irla"
},
{
"family": "Henry",
"given": "Jordan"
},
{
"family": "Hoter-Ishay",
"given": "Bat"
},
{
"family": "Mattison",
"given": "Courteney"
},
{
"family": "Starr",
"given": "Lindsey"
},
{
"family": "Lama",
"given": "Tsering"
},
{
"family": "Karaahmet",
"given": "Berke"
},
{
"family": "Cao",
"given": "Wenqing"
},
{
"family": "De Jager",
"given": "Philip L."
},
{
"family": "Taga",
"given": "Mariko"
},
{
"family": "Barnes",
"given": "Lisa L."
},
{
"family": "Marquez",
"given": "David X."
},
{
"family": "Bennett",
"given": "David A."
},
{
"family": "Zhang",
"given": "Ya"
},
{
"family": "Menon",
"given": "Vilas"
}
],
"container-title-short": "Nature",
"volume": "657",
"issue": "8130",
"page": "191-201",
"DOI": "10.1038/s41586-026-10793-0",
"PMID": "42457956",
"PMCID": "PMC13538069",
"ISSN": "0028-0836",
"publisher": "Nature Portfolio",
"URL": "https://doi.org/10.1038/s41586-026-10793-0",
"language": "en",
"issued": {
"date-parts": [
[
2026,
7,
15
]
]
}
}

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1038/s42003-026-10030-4 [code]
Cell-type-aware transcriptome-wide association studies identify 91 independent risk genes for Alzheimer's disease dementia.
Journal: Communications biology
In common: Alzheimer's / dementia, genetics / omics, cellular / molecular, 6 references, 2 authors
[2] doi:10.1016/j.celrep.2026.117235 [code]
Integration of aged brain multi-omics reveals cross-system mechanisms underlying Alzheimer's disease heterogeneity.
Journal: Cell reports
In common: Alzheimer's / dementia, genetics / omics, cellular / molecular, 11 references
[3] doi:10.1186/s13195-026-02081-w [code]
Cellular state heterogeneity underlying sex differences in Alzheimer's disease based on single-cell transcriptome.
Journal: Alzheimer's research & therapy
In common: Alzheimer's / dementia, genetics / omics, cellular / molecular, 9 references
[4] doi:10.1038/s41467-026-73007-1 [code]
Single-nucleus epigenomic dysregulation unmasks genetic risk-associated neurodegenerative glia states.
Journal: Nature communications
In common: Alzheimer's / dementia, genetics / omics, cellular / molecular, 8 references
[5] doi:10.1038/s43587-026-01204-0
Fibronectin mediates APOE4-driven blood-brain barrier dysfunction in Alzheimer's disease.
Journal: Nature aging
In common: Alzheimer's / dementia, genetics / omics, cellular / molecular, 4 references, author Philip L De Jager
[6] doi:10.1002/alz.71804
A meta-refined human Alzheimer's disease-associated gene subset shows partial mouse-model pathway correspondence and limited cross-cohort machine-learning transportability.
Journal: Alzheimer's & dementia : the journal of the Alzheimer's Association
In common: Alzheimer's / dementia, genetics / omics, cellular / molecular, 8 references
[7] doi:10.1093/braincomms/fcag326 [code]
Brain multiomic profiling identifies tau-related transcriptomic dysregulation in Alzheimer's disease.
Journal: Brain communications
In common: Alzheimer's / dementia, genetics / omics, cellular / molecular, 8 references
[8] doi:10.1016/j.isci.2026.117038 [code]
Multi-region brain transcriptomes uncover two subtypes of aging individuals with differences in Alzheimer risk and the impact of <i>APOEε4</i>.
Journal: iScience
In common: Alzheimer's / dementia, genetics / omics, cellular / molecular, 3 references, author Philip L De Jager
[9] doi:10.1038/s41467-026-74038-4 [code]
Semaglutide attenuates neuroinflammation in male mice.
Journal: Nature communications
In common: Alzheimer's / dementia, cellular / molecular, 8 references
[10] doi:10.1038/s41588-026-02722-8 [code]
A multiancestry polygenic risk score for Alzheimer's disease is associated with cognitive decline and neuropathological hallmarks in diverse populations.
Journal: Nature genetics
In common: Alzheimer's / dementia, genetics / omics, cellular / molecular, 6 references

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Sign in with ORCID to claim this paper as one of its authors, correct its record or validate its tracing map: when the paper's metadata lists your ORCID iD, you are recognized at once. Maintainers of its code: sign in with GitHub, then claim the repository on your account page.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion, reproductions, activity

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.