Cell-type signatures of Alzheimer’s disease shared across population groups
4 affiliations
- 1Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA
- 2Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA
- 3Department of Kinesiology and Nutrition, University of Illinois Chicago, Chicago, IL, USA
- 4Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA. [email protected]
Abstract
Genomic studies at single-cell resolution have implicated multiple cell types associated with clinical and pathological traits in Alzheimer’s Disease (AD), but have not examined common features across broad, multi-ethnic populations, and across multiple regions. To bridge this gap, we performed single-nucleus RNA-seq and ATAC-seq profiling of cortical and subcortical brain regions from post-mortem samples across Non-Latin White, African American, and Latin donors (the latter of any race). Using discrete and continuous dissection of molecular programs, we elucidate cell-type-specific glial and neuronal signatures associated with AD across multiple population groups. Notably, we found that multiple microglial ( GPNMB +, CD74 +, and CR1 + subgroups) and astrocyte ( SERPINH1 + and WIF1 + subgroups) signatures are associated with worse clinical and pathological phenotypes across all three population groups. We also report continuous gene expression factors in oligodendrocytes that are not captured by discrete clusters, yet still show strong associations with disease phenotypes. Finally, we observe these discrete cellular identities and continuous gene programs separate cognitively impaired donors into 6 molecularly distinct subgroups that span racial and ethnic population groups. Overall, our study identifies key cell types and gene programs implicated in AD that are shared across population groups, and provides an initial data set that underscores how representative sampling can capture conserved signatures as well as disease heterogeneity, leading to better prioritization of key cell types for further investigation.
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BibTeX
@article{luquez2026celltype,
title = {{Cell-type signatures of Alzheimer’s disease shared across population groups}},
author = {Tain Luquez and Jonathan Algoo and Rebecca Chiu and Jason A. Mares and Archana Yadav and Matti Lam and Pallavi Gaur and Xiaoying Lai and Dylan I. Lee and Fahad Paryani and Rafe Batchelor and I Belli and Jordan A. Henry and Bat Hoter-Ishay and Courteney Mattison and Lindsey A. Starr and Tsering Lama and Berke Karaahmet and Wenqing Cao and Philip L. De Jager and Mariko F. Taga and Lisa Laverne Barnes and David X. Márquez and David A. A Bennett and Ya Zhang and Vilas Menon},
journal = {Nature},
year = {2026},
month = jul,
doi = {10.1038/s41586-026-10793-0},
url = {https://doi.org/10.1038/s41586-026-10793-0},
note = {CC BY},
}
RIS
TY - JOUR
TI - Cell-type signatures of Alzheimer’s disease shared across population groups
AU - Tain Luquez
AU - Jonathan Algoo
AU - Rebecca Chiu
AU - Jason A. Mares
AU - Archana Yadav
AU - Matti Lam
AU - Pallavi Gaur
AU - Xiaoying Lai
AU - Dylan I. Lee
AU - Fahad Paryani
AU - Rafe Batchelor
AU - I Belli
AU - Jordan A. Henry
AU - Bat Hoter-Ishay
AU - Courteney Mattison
AU - Lindsey A. Starr
AU - Tsering Lama
AU - Berke Karaahmet
AU - Wenqing Cao
AU - Philip L. De Jager
AU - Mariko F. Taga
AU - Lisa Laverne Barnes
AU - David X. Márquez
AU - David A. A Bennett
AU - Ya Zhang
AU - Vilas Menon
PY - 2026
DA - 2026/07/15
JO - Nature
DO - 10.1038/s41586-026-10793-0
UR - https://doi.org/10.1038/s41586-026-10793-0
AB - Genomic studies at single-cell resolution have implicated multiple cell types associated with clinical and pathological traits in Alzheimer’s Disease (AD), but have not examined common features across broad, multi-ethnic populations, and across multiple regions. To bridge this gap, we performed single-nucleus RNA-seq and ATAC-seq profiling of cortical and subcortical brain regions from post-mortem samples across Non-Latin White, African American, and Latin donors (the latter of any race). Using discrete and continuous dissection of molecular programs, we elucidate cell-type-specific glial and neuronal signatures associated with AD across multiple population groups. Notably, we found that multiple microglial ( GPNMB +, CD74 +, and CR1 + subgroups) and astrocyte ( SERPINH1 + and WIF1 + subgroups) signatures are associated with worse clinical and pathological phenotypes across all three population groups. We also report continuous gene expression factors in oligodendrocytes that are not captured by discrete clusters, yet still show strong associations with disease phenotypes. Finally, we observe these discrete cellular identities and continuous gene programs separate cognitively impaired donors into 6 molecularly distinct subgroups that span racial and ethnic population groups. Overall, our study identifies key cell types and gene programs implicated in AD that are shared across population groups, and provides an initial data set that underscores how representative sampling can capture conserved signatures as well as disease heterogeneity, leading to better prioritization of key cell types for further investigation.
SN - 0028-0836
SN - 1476-4687
ER -