Cell type-specific associations with Alzheimer’s Disease conserved across racial and ethnic groups DOI Creative Commons

Tain Luquez,

Jonathan Algoo,

Rebecca Chiu

et al.

Published: April 15, 2025

Abstract Genomic studies at single-cell resolution have implicated multiple cell types associated with clinical and pathological traits in Alzheimer’s Disease (AD), but not examined common features across broad, multi-ethnic populations, regions. To bridge this gap, we performed single-nucleus RNA-seq ATAC-seq profiling of cortical subcortical brain regions from post-mortem samples Non-Latin White, African American, Latin donors (the latter any race). Using discrete continuous dissection molecular programs, elucidate cell-type-specific glial neuronal signatures AD population groups. Notably, found that microglial ( GPNMB +, CD74 CR1 + subgroups) astrocyte SERPINH1 WIF1 are worse phenotypes all three We also report gene expression factors oligodendrocytes captured by clusters, yet still show strong associations disease phenotypes. Finally, observe these cellular identities programs separate cognitively impaired into 6 molecularly distinct subgroups span racial ethnic Overall, our study identifies key shared groups, provides an initial data set underscores how representative sampling can capture conserved as well heterogeneity, leading to better prioritization for further investigation.

Language: Английский

Cell type-specific associations with Alzheimer’s Disease conserved across racial and ethnic groups DOI Creative Commons

Tain Luquez,

Jonathan Algoo,

Rebecca Chiu

et al.

Published: April 15, 2025

Abstract Genomic studies at single-cell resolution have implicated multiple cell types associated with clinical and pathological traits in Alzheimer’s Disease (AD), but not examined common features across broad, multi-ethnic populations, regions. To bridge this gap, we performed single-nucleus RNA-seq ATAC-seq profiling of cortical subcortical brain regions from post-mortem samples Non-Latin White, African American, Latin donors (the latter any race). Using discrete continuous dissection molecular programs, elucidate cell-type-specific glial neuronal signatures AD population groups. Notably, found that microglial ( GPNMB +, CD74 CR1 + subgroups) astrocyte SERPINH1 WIF1 are worse phenotypes all three We also report gene expression factors oligodendrocytes captured by clusters, yet still show strong associations disease phenotypes. Finally, observe these cellular identities programs separate cognitively impaired into 6 molecularly distinct subgroups span racial ethnic Overall, our study identifies key shared groups, provides an initial data set underscores how representative sampling can capture conserved as well heterogeneity, leading to better prioritization for further investigation.

Language: Английский

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