Race of people having blood tests for Alzheimer’s disease
According to a new study from the Washington University School of Medicine in St. Louis, three experimental blood tests used to identify people in the early stages of Alzheimer’s disease behave differently in blacks compared to whites.
The study showed that a fourth blood test – the PrecivityAD test, which is commercially available in the United States and Europe through C2N Diagnostics – was equally effective in detecting early Alzheimer’s disease, regardless of race of the person tested. Since the thresholds between normal and abnormal test results are usually defined based on predominantly white volunteers, tests that perform differently in black populations compared to white populations put black patients at a disproportionate risk of misdiagnosis. inappropriate diagnosis and medical care.
The study is published April 21 in the journal Neurology.
Most people are only diagnosed with Alzheimer’s disease after becoming forgetful and confused. These cognitive symptoms occur relatively late in the course of the disease, a decade or more after the brain begins to change. Scientists are working to identify people earlier using blood tests that detect proteins associated with Alzheimer’s disease in the blood, also known as biomarkers. But the field of Alzheimer’s biomarker research is based on data collected from predominantly white participant groups, raising concerns about whether tests based on these biomarkers are equally valid in diverse populations.
“When you use a limited study population – as, unfortunately, scientists have traditionally done in Alzheimer’s disease research – and then try to apply the results to everyone, including people from diverse backgrounds, you can exacerbate health inequities,” the lead author said. Suzanne Schindler, MD, Ph.D., associate professor of neurology. “I hope this article helps illustrate the need to increase the diversity of participants in Alzheimer’s disease studies. My colleagues and I are working to develop a much larger multicenter study to better assess racial differences in blood biomarkers related to Alzheimer’s disease. This is a major priority for us. »
The study was not designed to find why certain biomarkers of Alzheimer’s disease lead to different outcomes in blacks compared to whites, but the presence of other health conditions could play a role. In this study, black participants were more likely than white participants to have high blood pressure (67% versus 45%) and diabetes (28% versus 5%). Both conditions are linked to Alzheimer’s disease and may influence the performance of biomarker tests, the researchers said.
The PrecivityAD test uses high-resolution mass spectrometry to measure the ratio of amyloid beta 42 to amyloid beta 40 proteins, as well as apolipoprotein E (APOE), a protein that affects the risk of Alzheimer’s disease. The technology underlying the PrecivityAD test was developed at the University of Washington in the laboratory of Randall J. Bateman, MD, Charles F. and Joanne Knight Professor Emeritus of Neurology and co-author of this article. C2N, the maker of the PrecivityAD test, is a Washington University startup and is based in St. Louis.
The researchers analyzed the accuracy of the PrecivityAD test and blood tests for two other proteins – neurofilament light protein and two forms of tau protein – in 76 pairs of white, black, non-Hispanic participants. The pairs were created by drawing from a group of volunteers who participate in research studies through Charles F. and Joanne at the University of Washington. Knight Alzheimer’s Disease Research Center (Knight ADRC), and were matched on age, sex, cognitive status and the presence of the high-risk genetic variant of APOE. Over 90% of individuals had no cognitive impairment.
The researchers determined whether each individual had the brain changes of Alzheimer’s disease using brain scans, analyzing the cerebrospinal fluid that surrounds the brain and spinal cord, or both. High levels of amyloid plaques found on brain scans or specific changes in cerebrospinal fluid are both considered gold standard evidence of Alzheimer’s disease.
Only the PrecivityAD test accurately classified people by Alzheimer’s disease status, regardless of self-identified race. The other three blood tests were not as accurate at classifying people by Alzheimer’s disease status. Worse, they also behaved differently in black individuals compared to white individuals.
“The fact that these risk models have not been tested in many populations makes me suspicious, because Alzheimer’s disease is a global disease,” said co-author Thomas K. Karikari, PhD, assistant professor at Department of Psychiatry and Neurochemistry at the University of Gothenburg in Gothenburg, Sweden. Karikari is from Ghana. “For example, APOE is a strong predictor of Alzheimer’s disease in people of European ancestry, but for people of non-European ancestry it may not be a good predictor. We need to study these risk patterns in a wide variety of people to understand where it works, where it doesn’t, and what factors affect the performance of these patterns.
“Racial norming,” or calibrating tests separately for each race, is not a satisfactory solution to the problem of biomarker differences between racial groups, Schindler and Karikari said. Such a practice can create or aggravate racial disparities. For example, until 2021, the NFL routinely used race-based cognitive tests to assess former players for cognitive impairment related to injuries sustained on the field. These tests have consistently underestimated the degree of impairment suffered by black players, making it difficult for them to obtain proper compensation. University of Washington doctors don’t use racial norms when assessing cognitive function, says John C. Morris, MD, Harvey A. Emeritus Professor of Neurology and Dorismae Hacker Friedman. Morris is the director of Knight ADRC and co-author of the article.
“Rather than trying to adapt to race one way or another, it would be better to use tests that work equally well in all individuals,” Schindler said. “Alternatively, we can try to understand the underlying factors that create these apparent racial differences and adjust to those underlying factors rather than race. What we don’t want to do is use these tests without evaluating their performance in various groups, because then we would be failing in our duty to provide the best possible care to everyone.
The title of the article
Effect of race on the prediction of cerebral amyloidosis by plasma Aβ42/Aβ40, phosphorylated tau and neurofilament light.
Publication date of articles
Conflict of Interest Statement
SE Schindler received data on behalf of the University of Washington from C2N Diagnostics free of charge; TK Karikari reports no disclosures regarding the manuscript; NJ Ashton reports no disclosures regarding the manuscript; RL Henson reports no disclosures regarding the manuscript; KE Yarasheski is an employee of C2N Diagnostics, which offers the PrecivityADTM test described in this article; T. West is an employee of C2N Diagnostics, which offers the PrecivityADTM test described in this article; Mr. Meyer is an employee of C2N Diagnostics, which offers the PrecivityADTM test described in this article; KM Kirmess is an employee of C2N Diagnostics, which offers the PrecivityADTM test described in this article; Y. Li reports no disclosure of the manuscript; B. Saef reports no disclosure of the manuscript; KL Moulder reports no disclosure relevant to the manuscript; D. Bradford reports no disclosure relevant to the manuscript; AM Fagan has received research funding from Biogen, Centene, Fujirebio and Roche Diagnostics. She is a member of the Scientific Advisory Boards of Roche Diagnostics, Genentech and Diadem. She consults for DiamiR and Seimens Healthcare Diagnostics Inc.; BA Gordon does not report any disclosures regarding the manuscript; TLS Benzinger is supported by research funding initiated by researchers from the NIH, Alzheimer’s Association, Barnes-Jewish Hospital Foundation and Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly). She participates as a site investigator in clinical trials sponsored by Avid Radiopharmaceuticals, Eli Lilly, Biogen, Eisai, Jaansen and Roche. She is an unpaid consultant for Eisai and Siemens. She is on the Biogen Speakers Bureau; J. Balls-Berry is a member of the Patient Advisory Council and receives financial support for the project from Dartmouth University. RJ Bateman co-founded C2N Diagnostics. The University of Washington and Dr. Bateman own an interest in C2N Diagnostics and receive royalties based on technology (stable isotope labeling kinetics and blood plasma analysis) licensed from the University of Washington to C2N Diagnostics. He receives income from C2N Diagnostics for serving on the Scientific Advisory Board. The University of Washington, with Dr. Bateman as co-inventor, has filed the US Provisional Patent Application “Plasma Based Methods for Detecting CNS Amyloid Deposition”. He is a consultant for Roche, Genentech, AbbVie, Pfizer, Boehringer-Ingelheim and Merck; C. Xiong consults for Diadem; H. Zetterberg has served on scientific advisory boards and/or as a consultant for Alector, Eisai, Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics, Nervgen, AZTherapies, CogRx and Red Abbey Labs, has given lectures at symposia sponsored by Cellectricon, Fujirebio, Alzecure and Biogen, and is co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), part of the GU Ventures incubator program; K. Blennow has served as a consultant, on advisory boards or data monitoring committees for Abcam, Axon, Biogen, JOMDD/Shimadzu. Julius Clinical, Lilly, MagQu, Novartis, Prothena, Roche Diagnostics and Siemens Healthineers, and is co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), part of the GU Ventures incubator program; JC Morris, MD is the Chair of the Cure Alzheimer Fund Strategic Research Council.
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