
A shared molecular signature of Alzheimer’s appears across populations once studied in isolation.
Alzheimer’s disease (AD) affects African Americans (AA) at roughly twice the rate seen among White/European-ancestry (EA) individuals in the United States. This disparity is partly linked to social determinants of health, including unequal access to health care, differences in educational quality, biases in cognitive testing, and higher prevalence of AD risk factors such as cardiovascular disease and diabetes among people who identify as African American.
Research has explored how gene expression (measure of the amount of protein encoded by a gene) differs between brain tissue from people with AD and those without the disease, most often in EA or mixed ancestry populations. However, many of these studies included too few AA participants, or did not specify their numbers, making it difficult to detect meaningful patterns specific to this group.
Large-scale brain expression analysis
In the largest study of its kind using brain tissue from AA donors, scientists at Boston University Chobanian & Avedisian School of Medicine identified numerous genes whose activity levels differed between AD cases and controls. Many of these genes had not been previously linked to AD through other genetic research. The most striking result was a 1.5-fold increase in expression of the ADAMTS2 gene in brain tissue from individuals with autopsy-confirmed AD.
To conduct the analysis, the team collected post-mortem prefrontal cortex samples from 207 AA brain donors through 14 NIH-funded AD Research Centers nationwide. This group included 125 donors with pathologically confirmed AD and 82 controls. ADAMTS2 emerged as the most significantly altered gene and was also ranked highest in a separate study led by the same researchers who analyzed brain tissue from a much larger EA cohort. In that work, gene expression was compared between people with confirmed AD who showed cognitive symptoms before death and those with similar brain pathology who remained cognitively resilient.
Cross-ancestry convergence and implications
“To our knowledge, this is the first time in similarly designed AD genetics studies that the most significant finding was the same in both white and African Americans,” said corresponding author Lindsay A. Farrer, PhD, chief of biomedical genetics at the school.
According to the researchers, this study is an important step in deciphering the genetic architecture and underlying mechanisms of AD risk in African Americans, considering evidence that nearly all the established AD risk variants are population-specific or have divergent frequencies across populations.
“Although risk of AD in African Americans has been associated with variants in several genes, the overlap of genes showing association in EA populations is modest, and even among the overlapping genes, the particular variants involved and the size of the effect on AD risk usually differ,” explains Farrer. “The fact that expression of ADAMTS2 is significantly and substantially higher in brain tissue from both Whites and Blacks with AD not only points to a shared biological process leading to AD, but also elevates the priority of further research involving this gene which could determine its suitability as a potential therapeutic target.”
References:
“Novel differentially expressed genes and multiple biological pathways for Alzheimer’s disease identified in brain tissue from African American donors” by 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 and Lindsay A. Farrer, 8 October 2025, Alzheimer’s & Dementia.
DOI: 10.1002/alz.70629
“Transcriptome Signatures for Cognitive Resilience Among Individuals with Pathologically Confirmed Alzheimer Disease” by Donghe Li, Xudong Han, Lindsay A. Farrer, Thor D. Stein and Gyungah R Jun, 3 January 2025, Alzheimer’s & Dementia.
DOI: 10.1002/alz.090972
This study was supported by National Institute of Health grants R01-AG048927, U01-AG058654, U54-AG052427, U19-AG068753, U01-AG062602, P30-AG072978, U01-081230, P01-AG003949, P30-AG062677, P30-AG062421; P30-AG 066507, P30-AG066511, P30-AG 072972, P30-AG066468, R01-AG072474, RF1-AG066107, U24-AG056270, P01-AG003949 , RF1-AG082339, RF1-NS118584, P30-AG072946; P01-AG003991, P30-AG066444, P01-AG026276, P30-AG066462, P30-AG072958, and P30-AG072978, and by Florida Department of Health awards 8AZ06 and 20A22. The funding sources had no role in study design; in the collection, analysis or interpretation of data; in the writing of this article; or in the decision to submit this article for publication.
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6 Comments
My strong suspicion is that Alzheimer’s came about due to the increasingly common ingestion of highly processed foods. Foods our bodies aren’t even sure how to handle because they are foreign and something not found in nature. Add in the use of microwaves to cook and heat our food that breaks down the molecules in an unnatural way.Add in all the medications we are prescribed in an ever dizzying pace. Is it any wonder!
Blacks have as much, if not more, access to quality medical services than the average person because most of them are on Medicaid. Their every illness can be promptly taken care of. The disparity is that they neglect their symptoms and don’t take prescribed meds as per instruction. Their unhealthy pamdiet and lifestyle are major contributors to their poor health.
I beg to differ. Most people I know who are on Medicaid are white and disabled. When I visit them in homes most of the residents are white and have a disability.
The first paragraph tries to force us into believing that black people get twice as much Alzheimer’s because of inequality, then the rest of the article tells us it’s actually because of a “1.5-fold increase in expression of the ADAMTS2 gene in brain tissue”. Virtue Signaling garbage.
I do not believe that “most Blacks” are on Medicaid. Please provide the source with a link to support your assertion.
Also, please provide the source for your assertion that Black people don’t get readily available medical care and don’t take prescription medications as prescribed.
Generalized statements about an entire group of people are generally FALSE. And, such statements sound racist.
No one in this thread has said ‘most blacks’ in fact they said more blacks have access to better health care. A simple fact in the US. A simple Google search will inform you that the black population is 12% while they make up over 25% of benefit recipients. Disproportionately More so than any other demographic in the US while crying a lack of access. Now I do agree that our medicare system should be a bit better. For example how low the poverty line is in major cities is ubsurd. However saying people are saying ‘most blacks’ well no one here has said it. What people HAVE said is we KNOW they disproportionately get benefits over poor other demographics. In fact it’s easy to argue how absurdly racist this new school ‘blacks have it bad’ culture the left wants to push as a clear delusion and attempt to raise their own status. Blacks DO NOT have it ‘worse’ than their white counterparts in similar financial situations, claiming as a white you have it better is actually beyond racist. And entirely untrue.