Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
Novel differentially expressed genes and multiple biological pathways for Alzheimer's disease identified in brain tissue from African American donors.
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Logue Mark W, Labadorf Adam, O'Neill Nicholas K, Dickson Dennis W, Dugger Brittany N, Flanagan Margaret E, Frosch Matthew P, Gearing Marla, Jin Lee-Way, Kofler Julia, Mayeux Richard, McKee Ann, Miller Carol A, Murray Melissa E, Nelson Peter T, Perrin Richard J, Schneider Julie A, Stein Thor D, Teich Andrew F, Tobunluepop Katarnut, Troncoso Juan C, Wang Shih-Hsiu, Wang Zihan, Wolozin Benjamin, Mez Jesse, Farrer Lindsay A
Аннотация
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.
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.