African-Americans have lower expression of two biomarkers of Alzheimer’s, suggesting a possible race-dependent biological mechanism that contributes to the development of the disease, a study shows.
This discrepancy between African-American and white patients is particularly relevant for those who carry the ApoE4 variant of the ApoE gene.
The study, “Assessment of Racial Disparities in Biomarkers for Alzheimer Disease,” was published in the journal JAMA neurology.
African-Americans represent 13.3 percent of the population in the United States. However, they are often under-represented in the patient populations included in Alzheimer’s disease clinical trials, which are largely formed by white research volunteers.
While some prior studies have investigated potential racial differences in Alzheimer’s — particularly between African-Americans and non-Hispanic white individuals — results are often conflicting. For example, some studies have found that African-Americans are at a higher risk of developing dementia and Alzheimer’s, while other studies have not found any racial differences.
Similar discrepancies exist in studies that have attempted to investigate whether there are any differences in the biological mechanisms underlying Alzheimer’s disease between African-Americans and white individuals. In particular, little is known about any potential differences in the expression of molecular biomarkers of disease. A biomarker is a measurable substance in an organism that is indicative of a disease.
Alzheimer’s disease is characterized by the presence of harmful aggregates of proteins such as amyloid-beta and tau. These proteins, which serve as Alzheimer’s biomarkers, can be identified through positron emission tomography (PET) imaging of the brain or by measuring concentrations of these proteins in the cerebrospinal fluid (CSF) — the fluid found in the brain and spinal cord.
If Alzheimer’s biomarkers do differ between races, gaining insight into these differences could lead to the implementation of race-dependent thresholds for biomarker positivity that could be used in research studies, including screening for clinical trials of experimental therapies.
In this study, researchers at Washington University in St. Louis investigated any potential race-dependent differences in biomarker expression in Alzheimer’s disease. The team reviewed molecular biomarker data from 1,255 participants in a study of healthy aging and Alzheimer’s disease, of whom 173 were African-American.
Participants completed a magnetic resonance imaging (MRI) study of the brain, PET imaging, and/or cerebrospinal fluid (CSF) assays to determine concentrations of three Alzheimer’s biomarkers — amyloid-beta, total tau, and phosphorylated tau — a chemically modified form of the tau protein associated with Alzheimer’s development.
Researchers analyzed the data while taking into account age, sex, educational level, race, the presence of the gene variant apolipoprotein E4 (ApoE4), and clinical status (normal cognition or dementia). The presence of ApoE4, a specific form of the ApoE gene, is associated with a higher risk of developing Alzheimer’s.
A total of 116 out of the 173 African-American participants (67.1%) and 724 out of the 1,082 non-Hispanic white participants (66.9%) had normal cognition.
No racial differences were found regarding the frequency of cerebral ischemic lesions (restricted blood flow to the brain, a marker of neurodegeneration), amyloid-beta accumulation in the brain, or amyloid-beta concentrations in the CSF.
However, in individuals with a reported family history of dementia, the mean total hippocampal volumes were lower for African-American participants than for white participants. The hippocampus is the region of the brain responsible for forming new memories, so a smaller hippocampal volume is responsible for short-term memory loss in Alzheimer’s patients.
Mean CSF concentrations of total tau were lower in African-American participants than in non-Hispanic white participants, as were mean concentrations of phosphorylated tau. Interestingly, this was found to be related to ApoE4 status, as only individuals who were ApoE4 carriers showed these racial differences.
“The results of this study suggest that analyses of molecular biomarkers of Alzheimer disease should adjust for race,” the researchers wrote.
In particular, the authors suggest there should be a lower threshold for CSF concentrations of total tau and phosphorylated tau in African-American individuals, especially those who are ApoE4-positive.