Impact of Racial Differences in Alzheimer Biomarkers

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RESEARCH UPDATE
Cognitive impairment in older African Americans is associated with smaller changes in cerebrospinal fluid (CSF) tau biomarkers but greater impact from white matter hyperintensity (WMH) burden compared with impairment in older white Americans, according to a study from Emory University in Atlanta, Georgia.¹

These race-associated differences in CSF tau markers may result in underdiagnosis of Alzheimer disease (AD) in African Americans, according to the research team. This is the first study to directly look at race, CSF AD biomarker levels, and the relationships between WMH and cognition.

Background
The researchers noted that the prevalence of AD is nearly doubled in African Americans compared with whites. Although African Americans also reportedly are more likely than whites to have nonamnestic forms of mild cognitive impairment (MCI) and slower decline to and through dementia, postmortem studies show that they have greater ischemia, which is associated with WMH burden, and Lewy body copathology.

Study design
The Emory team hypothesized that CSF amyloid biomarkers, neurodegeneration, and endothelial dysfunction would differ between older black and white Americans with normal cognition and AD-associated cognitive impairment. They prospectively recruited older black and white Americans with either normal cognition, MCI, or AD to explore race-related differences in efforts to improve the characterization of AD and non-AD pathology in older African Americans.

A total of 65 older black and 70 older white Americans (average age, 70 years for both cohorts) were enrolled in the study and underwent detailed clinical, neuropsychological, MRI, genetic, and CSF analyses. Aβ40 and Aβ42, tau, neurodegenerative and candidate endothelial markers, and soluble intercellular cell adhesion molecule 1 were characterized to test their association with cognitive impairment within each race.

Results
The research team found that African Americans were significantly more likely than whites to have the ABCA7 risk allele (47% vs 23%; P = .005) and the ICAM1 Lys56-Met polymorphism (33% vs 6%; P <.001). They also were significantly more likely to have hypertension (72% vs 46%; P = .003) and diabetes (34% vs 6%; P < .001). The 2 groups were otherwise similar regarding age, sex, other vascular risk factors, Aβ42 levels, presence of the neurofilament light chain marker, and WMH and hippocampal volumes. African American participants also had significantly lower CSF levels of p-tau181 (17.9 vs 25.6 pg/mL; P <.001), t-tau (47.0 vs 71.5 pg/mL; P = .001), and Aβ40 (7.88 vs 9.29 ng/mL; P = .017).

In reviewing vascular influences, the team found that whereas the endothelial marker sVCAM-1 correlated with known vascular disease markers in whites, it was a poor measure of endothelial dysfunction in African Americans. The researchers then examined biomarker variables that influence cognitive Z-scores and found that APOE and ABCA7 genotypes, log₁₀ (WMH), and CSF levels of Aβ42 and t-tau play a role. Analysis that involved interaction between race and log₁₀ (WMH) showed an association between black race, log₁₀ (WMH), and greater cognitive impairment with every increased unit of change. Black race was associated with a lower cognitive Z-score (by 0.496; P = .006) per unit change of log (WMH).

The bottom line
Given these findings, the researchers concluded that CSF neurodegenerative and endothelial markers do not account for race-associated AD biomarker differences. Rather, they conjectured that the same degree of WMH in black and white persons may have a greater impact on cognition in the former, although the mechanism needs elucidation.

The researchers explained that WMH burden is thought to be a consequence of terminal organ damage from chronic ischemia to which black persons may be more predisposed. They also conjectured that brain amyloid deposition in black persons may preferentially enhance WMH-associated neurotoxicity.

References:

1. Howell JC, Watts KD, Parker MW, et al. Race modifies the relationship between cognition and Alzheimer’s disease cerebrospinal fluid biomarkers. Alzheimers Res Ther. 2017;9:88.