Journal Article

Novel differentially expressed genes and multiple biological pathways for Alzheimer's disease identified in brain tissue from African American donors

Schneider, Julie A., Stein, Thor D., Mez, Jesse, Dickson, Dennis W., McKee, Ann, Miller, Carol A., Labadorf, Adam, Wang, Zihan, Farrer, Lindsay A., Frosch, Matthew P., Mayeux, Richard, Gearing, Marla, Jin, Lee‐Way, Tobunluepop, Katarnut, Logue, Mark W., Perrin, Richard J., Flanagan, Margaret E., Nelson, Peter T., Kofler, Julia, O'Neill, Nicholas K., Dugger, Brittany N., Troncoso, Juan C., Murray, Melissa E., Wolozin, Benjamin, Teich, Andrew F., Wang, Shih‐Hsiu

2025

Overview

INTRODUCTION Few African American (AA) donors have been included in post mortem Alzheimer's disease (AD) studies compared to European‐ancestry (EA) individuals. METHODS We generated transcriptome‐wide bulk pre‐frontal cortex (PFC) gene expression data from 125 AA donors with neuropathologically determined AD and 82 AA controls. RESULTS Transcriptome‐wide significant differential expression was observed with 482 genes. The most significant, ADAMTS2, showed 1.52 times higher expression in AD cases (p = 2.96x10−8). Comparison of findings with those from a recent gene expression study of EA brain donors revealed substantial concordance, including ADAMTS2. Other associations not observed in EA results may be especially relevant to AD risk in the AA population. Examination of AA AD GWAS‐implicated variants identified several expression quantitative trait loci. CONCLUSION This first large‐scale AA brain AD gene expression study identified many differentially expressed genes, including ADAMTS2, and supports gene expression as a molecular pathway underlying the impact of several AA AD risk variants. Highlights We performed the largest African American brain tissue Alzheimer's disease (AD) gene expression study. Expression differences for 482 genes, notably ADAMTS2, were study‐wide significant. Many significant differentially expressed genes are involved in energy metabolism. Several previously known AD‐associated variants in African Americans are eQTLs. These results advance knowledge of the genetic basis of AD in the AA population.

• Publisher: Wiley
• Subject: ADAMTS2 / African American / Aged / Aged, 80 and over / Alzheimer disease / Alzheimer Disease - genetics / Alzheimer Disease - metabolism / Alzheimer Disease - pathology / Black or African American - genetics / Brain - metabolism / Brain - pathology / differential gene expression / eQTL / Female / gene network analysis / Genetic Predisposition to Disease / Genome-Wide Association Study / Humans / Male / Middle Aged / Tissue Donors / Transcriptome / White