Race May Impact Expression of Alzheimer’s Biomarkers

The toxic buildup of the proteins amyloid-β and tau is a hallmark feature of brains affected by Alzheimer’s disease (AD). A study published January 7 in JAMA Neurology now reveals that the accumulation of tau may vary with race. A research team at Washington University School of Medicine in St. Louis found that African Americans, whether they have Alzheimer’s or not, have about one-third less tau on average than whites.

“To our knowledge, our study is the first to examine racial differences in molecular biomarkers of AD in which the cohort contributed data for both amyloid concentrations as seen on PET [positron emission tomography] scan and CSF [cerebrospinal fluid] concentrations of [amyloid and tau],” wrote lead author John C. Morris, M.D., a professor of neurology at Washington University’s Knight Alzheimer Disease Research Center, and colleagues. “Understanding how race may modify the risk and expression of AD may yield new insights into race-dependent biological mechanisms that in turn can inform future diagnostics and therapeutic advances.”

Morris and colleagues analyzed data from 1,255 adults aged 43 or older who were participating in Alzheimer’s studies at the Knight Research Center; this sample included 173 African Americans and 1,082 non-Hispanic whites. As part of these studies, the participants received brain scans and provided CSF samples.

The researchers found no racial differences between African Americans and whites when it came to the average amyloid levels, whether measured in CSF or on PET scans. This was true even after adjusting for differences in sex, educational level, Alzheimer’s family history, body mass index, and degree of cognitive impairment between the groups.

Compared with white participants, African-American participants were found to have significantly lower CSF levels of tau (brain scans of tau were not taken). Average CSF concentrations of tau were 294 pg/mL for African Americans and 443 pg/mL for whites. This discrepancy in tau levels was even greater among participants who had the Alzheimer’s risk gene APOEε4. Among APOEε4 carriers, average tau concentrations were 270 pg/mL for African Americans and 464 pg/mL for whites.

Recent studies have shown that APOEε4 may influence tau-related neurological damage. Morris said that his group’s findings suggest that APOEε4 and tau interact differently in African Americans and whites.

“Caution is needed in interpreting our results until they can be confirmed (or refuted) with subsequent analyses in larger cohorts to carefully explore the influences of socioeconomic status, comorbid diseases, and other factors that may contribute to racial differences,” the researchers wrote.

Tau concentrations were not the only differences between the two groups that were uncovered by Morris and colleagues. Analysis of MRI scans of the participants revealed that African Americans had smaller hippocampal volumes on average than whites. The hippocampus is a brain region that plays a key role in memory, and studies have found an association between smaller hippocampal volumes and Alzheimer’s risk. This difference was most pronounced between African Americans and whites who had a family history of dementia.

“Inclusion of African-American individuals and other minority populations in biomarker studies is challenging, even for research centers that do this work well,” wrote Lisa Barnes, Ph.D., the Alla V. and Solomon Jesmer Professor of Gerontology and Geriatric Medicine at Rush University Medical Center in an editorial accompanying the study. “But as the field moves toward a biological definition of AD, the underinclusion of minority populations in AD research will significantly hinder our progress as a field, and the race to end AD will not be shared with our most vulnerable, at-risk populations.”

This study was supported by grants from the National Institute on Aging and the National Center for Advancing Translational Sciences. ■

“Assessment of Racial Disparities in Biomarkers for Alzheimer Disease” can be accessed here. The editorial, “Biomarkers for Alzheimer Dementia in Diverse Racial and Ethnic Minorities—A Public Health Priority,” is available here.