Mark W. Logue, Adam Labadorf, Nicholas K. O'Neill, Dennis W. Dickson, Brittany N. Dugger, Margaret E. Flanagan, Matthew P. Frosch, Marla Gearing, Lee-Way Jin, Julia Kofler, Richard Mayeux, Ann McKee, Carol A. Miller, Melissa E. Murray, Peter T. Nelson, Richard J. Perrin, Julie A. Schneider, Thor D. Stein, Andrew F. Teich, Katarnut Tobunluepop, Juan C. Troncoso, Shih-Hsiu Wang, Zihan Wang, Benjamin Wolozin, Jesse Mez, Lindsay A. Farrer
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Farrer","doi":"10.1002/alz.70629","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> INTRODUCTION</h3>\n \n <p>Few African American (AA) donors have been included in <i>post mortem</i> Alzheimer's disease (AD) studies compared to European-ancestry (EA) individuals.</p>\n </section>\n \n <section>\n \n <h3> METHODS</h3>\n \n <p>We generated transcriptome-wide bulk pre-frontal cortex (PFC) gene expression data from 125 AA donors with neuropathologically determined AD and 82 AA controls.</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p>Transcriptome-wide significant differential expression was observed with 482 genes. The most significant, <i>ADAMTS2</i>, showed 1.52 times higher expression in AD cases (<i>p</i> = 2.96x10<sup>−8</sup>). Comparison of findings with those from a recent gene expression study of EA brain donors revealed substantial concordance, including <i>ADAMTS2</i>. 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.</p>\n </section>\n \n <section>\n \n <h3> CONCLUSION</h3>\n \n <p>This first large-scale AA brain AD gene expression study identified many differentially expressed genes, including <i>ADAMTS2</i>, and supports gene expression as a molecular pathway underlying the impact of several AA AD risk variants.</p>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>We performed the largest African American brain tissue Alzheimer's disease (AD) gene expression study.</li>\n \n <li>Expression differences for 482 genes, notably <i>ADAMTS2</i>, were study-wide significant.</li>\n \n <li>Many significant differentially expressed genes are involved in energy metabolism.</li>\n \n <li>Several previously known AD-associated variants in African Americans are eQTLs.</li>\n \n <li>These results advance knowledge of the genetic basis of AD in the AA population.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1000,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70629","citationCount":"0","resultStr":"{\"title\":\"Novel differentially expressed genes and multiple biological pathways for Alzheimer's disease identified in brain tissue from African American donors\",\"authors\":\"Mark W. 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Novel differentially expressed genes and multiple biological pathways for Alzheimer's disease identified in brain tissue from African American donors
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.
期刊介绍：
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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