Race Differences Seen in Alzheimer Biomarkers

Concentrations of tau protein and its phosphorylated isoform in cerebrospinal fluid (CSF) differed significantly between African-American and white individuals, researchers found.

Mean CSF concentrations of total tau were lower in African-American participants than in white participants (293.65 vs 443.28 pg/mL, P<0.001), as were mean concentrations of phosphorylated tau (53.18 vs 70.73 pg/mL, P<0.001), reported John Morris, MD, of the Washington University School of Medicine in St. Louis, and colleagues.

Only participants with an APOE ε4 allele showed these differences, suggesting a significant race-by-APOE ε4 interaction, they wrote in JAMA Neurology. There was no difference between African-American and white participants for CSF concentrations of the 42-residue form of amyloid beta protein.

There are at least three major implications of these findings, Morris said.

“First, in almost all studies of molecular biomarkers of Alzheimer disease, the findings from amyloid PET imaging and assays of cerebrospinal fluid concentrations of Alzheimer’s proteins have been analyzed without regard to the racial or ethnic origins of individual research participants — that is, the findings have simply been pooled, with the assumption that everyone is the same,” he told MedPage Today. But “at least for tau biomarkers, race-specific analyses and cut-offs are needed.”

Second, differences in CSF total tau and phosphorylated tau levels may indicate differences in biological mechanisms underlying Alzheimer’s disease between African-American and white individuals.

Third, the results “underscore the fact that, as a research community, we need to do a much better job of being welcoming to people of color,” Morris said. “Almost everything we’ve learned about Alzheimer’s disease in the past 35 years has come from studies in research participants who were almost totally white.”

“As the U.S. population is becoming increasingly diverse, our research populations need to reflect that diversity,” he stated. “Otherwise, what we learn about the disease and how to effectively treat it may apply only to white people.”

Previous data about APOE ε4 and Alzheimer’s in African-American individuals have been mixed, with most — but not all — studies showing a weaker effect of APOE ε4 in this population, despite the allele being much more frequent, said Lisa Barnes, PhD, of Rush University Medical Center in Chicago, in an accompanying editorial.

“The APOE ε4 allele has been found to be the most robust driver of Alzheimer’s disease pathologic characteristics in white individuals,” she wrote. “Given the weaker association of APOE ε4 with risk of Alzheimer’s disease in African-American individuals, however, one would have expected the association with pathologic characteristics to be weaker as well, consistent with what the study by Morris and colleagues reported.”

In an earlier study Barnes co-authored, APOE ε4 in African-American individuals was related to a faster rate of decline in episodic memory compared to white individuals but not in other cognitive domains, suggesting the weakened effect of this allele may stem from brief global measures that may obscure its specific effect on episodic memory, she added.

Morris and colleagues used biomarker data from 1,255 adults enrolled in longitudinal studies at the Knight Alzheimer Disease Research Center at Washington University who had at least one Alzheimer’s biomarker study from 2004 to 2015. Participants averaged about age 71 and 173 people (13.8%) were African-American. Two-thirds had normal cognition; the remaining one-third were in the earliest stages of Alzheimer’s disease.

Besides reduced CSF levels of total tau and phosphorylated tau, African-American participants with a reported family history of dementia had lower hippocampal volumes than white individuals (6,418.26 vs 6,990.50 mm³, P<0.001). The APOE ε4 allele was associated with increased amyloid PET imaging standardized uptake value ratio in both African-American and white individuals.

Sample sizes varied significantly across different biomarker categories: African-American individuals were as likely as white individuals to have MRI data but less likely to have CSF data, and PET imaging was low for both groups, Barnes observed.

“It is not clear how differential participation across biomarkers may have influenced the reported results, as persons agreeing to undergo the various procedures were likely not random,” she wrote. And other factors — including socioeconomic status, comorbid diseases, and negative cultural experiences — that may contribute to racial differences in Alzheimer’s and cognitive impairment might have influenced results but were not included as covariates, she added.

This study also is limited by its cross-sectional nature: biomarkers could not be tied to Alzheimer’s progression, Morris and colleagues noted. People participating in Alzheimer’s biomarker studies are not representative of the overall population and results may not be applicable to others. Findings should be interpreted with caution until they can be confirmed or refuted with larger studies, they added.