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

Key Points:

• The study analyzed post-mortem brain tissue from 167 diverse participants without known dementia at enrollment, sourced from ROSMAP, MARS, and Latino Core Study cohorts, with detailed clinicopathological and cognitive decline data.
• Single-nucleus multiomic data (snRNA-seq and snATAC-seq) were generated from three brain regions (DLPFC, STG, AC) using the 10x Genomics Chromium platform, followed by rigorous quality control, clustering, and donor demultiplexing based on genetic variants.
• Statistical analyses included compositional modeling of cell-type proportions and gene expression factors associated with Alzheimer's disease pathology and cognitive decline, employing multiple methods and meta-analyses across population groups.
• Spatial transcriptomics using Xenium multiplexed in situ hybridization validated cell-type distributions and gene expression patterns in brain tissue sections, complementing single-cell data.
• Genetic ancestry was estimated using whole-genome sequencing data, and polygenic risk scores for Alzheimer's disease were computed to disentangle genetic and environmental contributions to observed molecular and clinical phenotypes.