Home > Publications Database > The Caribbean-Hispanic Alzheimer's disease brain transcriptome reveals ancestry-specific disease mechanisms. > print

001     169129
005     20240403131746.0
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024 7 _ |a 10.1016/j.nbd.2022.105938
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024 7 _ |a 0969-9961
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024 7 _ |a 1095-953X
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037 _ _ |a DZNE-2023-00008
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Felsky, Daniel
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245 _ _ |a The Caribbean-Hispanic Alzheimer's disease brain transcriptome reveals ancestry-specific disease mechanisms.
260 _ _ |a [Amsterdam]
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|b Elsevier
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520 _ _ |a 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.
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650 _ 7 |a Alzheimer's disease
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650 _ 7 |a Brain gene expression
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650 _ 7 |a Bulk tissue
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650 _ 7 |a Caribbean-Hispanic
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650 _ 7 |a Single cell
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650 _ 7 |a SORL1 protein, human
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650 _ 7 |a LDL-Receptor Related Proteins
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650 _ 7 |a Membrane Transport Proteins
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Transcriptome
|2 MeSH
650 _ 2 |a Alzheimer Disease: genetics
|2 MeSH
650 _ 2 |a Caribbean People
|2 MeSH
650 _ 2 |a Ethnicity
|2 MeSH
650 _ 2 |a Brain
|2 MeSH
650 _ 2 |a Genetic Predisposition to Disease
|2 MeSH
650 _ 2 |a Polymorphism, Single Nucleotide
|2 MeSH
650 _ 2 |a LDL-Receptor Related Proteins: genetics
|2 MeSH
650 _ 2 |a Membrane Transport Proteins: genetics
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700 1 _ |a Santa-Maria, Ismael
|b 1
700 1 _ |a Cosacak, Mehmet Ilyas
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700 1 _ |a French, Leon
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700 1 _ |a Schneider, Julie A
|b 4
700 1 _ |a Bennett, David A
|b 5
700 1 _ |a De Jager, Philip L
|b 6
700 1 _ |a Kizil, Caghan
|0 P:(DE-2719)2811030
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700 1 _ |a Tosto, Giuseppe
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|e Corresponding author
773 _ _ |a 10.1016/j.nbd.2022.105938
|g Vol. 176, p. 105938 -
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|t Neurobiology of disease
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|y 2023
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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