Journal Article

DZNE-2023-00008

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The Caribbean-Hispanic Alzheimer's disease brain transcriptome reveals ancestry-specific disease mechanisms.

Felsky, D. ; Santa-Maria, I. ; Cosacak, M. I.DZNE* ; French, L. ; Schneider, J. A. ; Bennett, D. A. ; De Jager, P. L. ; Kizil, C.DZNE* ; Tosto, G. (Corresponding author)

2023
Elsevier [Amsterdam]

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Please use a persistent id in citations: doi:10.1016/j.nbd.2022.105938

Abstract: Identifying ancestry-specific molecular profiles of late-onset Alzheimer's Disease (LOAD) in brain tissue is crucial to understand novel mechanisms and develop effective interventions in non-European, high-risk populations. We performed gene differential expression (DE) and consensus network-based analyses in RNA-sequencing data of postmortem brain tissue from 39 Caribbean Hispanics (CH). To identify ancestry-concordant and -discordant expression profiles, we compared our results to those from two independent non-Hispanic White (NHW) samples (n = 731). In CH, we identified 2802 significant DE genes, including several LOAD known-loci. DE effects were highly concordant across ethnicities, with 373 genes transcriptome-wide significant in all three cohorts. Cross-ancestry meta-analysis found NPNT to be the top DE gene. We replicated over 82% of meta-analyses genome-wide signals in single-nucleus RNA-seq data (including NPNT and LOAD known-genes SORL1, FBXL7, CLU, ABCA7). Increasing representation in genetic studies will allow for deeper understanding of ancestry-specific mechanisms and improving precision treatment options in understudied groups.

Keyword(s): Humans (MeSH) ; Transcriptome (MeSH) ; Alzheimer Disease: genetics (MeSH) ; Caribbean People (MeSH) ; Ethnicity (MeSH) ; Brain (MeSH) ; Genetic Predisposition to Disease (MeSH) ; Polymorphism, Single Nucleotide (MeSH) ; LDL-Receptor Related Proteins: genetics (MeSH) ; Membrane Transport Proteins: genetics (MeSH) ; Alzheimer's disease ; Brain gene expression ; Bulk tissue ; Caribbean-Hispanic ; Single cell ; SORL1 protein, human ; LDL-Receptor Related Proteins ; Membrane Transport Proteins

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Contributing Institute(s):

1. Mechanisms of induced plasticity of the vertebrate brain (AG Kizil)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2023

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