Abstract
BackgroundAfrican Americans have been reported to have a higher prevalence of Alzheimer’s disease (AD) than Caucasians, but etiology-specific AD biomarkers have not been systematically analyzed in older African Americans. Coexisting cerebrovascular disease may also contribute to this increased prevalence. We hypothesized that cerebrospinal fluid (CSF) biomarkers of amyloid, neurodegeneration, and endothelial dysfunction would differ between older African Americans and Caucasians with normal cognition and cognitive impairment associated with AD.MethodsWe prospectively recruited 135 older Americans to undergo detailed clinical, neuropsychological, genetic, magnetic resonance imaging (MRI), and CSF analysis from 2013 to 2015 at Emory University (Atlanta, GA, USA). We compared levels of CSF markers for β-amyloid (Aβ42, Aβ40), total and phosphorylated tau (t-tau and p-tau181, respectively), endothelial dysfunction (soluble vascular cell adhesion molecule 1, soluble intercellular adhesion molecule 1), α-synuclein, and neurodegeneration (neurofilament light chain [NfL]), as well as MRI markers, for hippocampal atrophy and cerebrovascular disease (white matter hyperintensity [WMH] volume).ResultsSixty-five older African Americans (average age, 69.1 years) and 70 older Caucasians (average age, 70.8 years) were included. After adjusting for demographic variables, AD risk alleles, and cognitive function, older African Americans had lower CSF levels of p-tau181 (difference of 7.4 pg/ml; 95% CI, 3.7–11.2 pg/ml; p < 0.001), t-tau (difference of 23.6 pg/ml; 95% CI, 9.5–37.7; p = 0.001), and Aβ40 (difference of 1.35 ng/ml; 95% CI, 0.29–2.42 ng/ml; p = 0.013) despite similar levels of Aβ42, NfL, WMH volume, and hippocampal volume. Cognitively impaired African Americans also had lower CSF t-tau/Aβ42 (difference of 0.255 per 1-SD change in composite cognition; 95% CI, 0.100–0.409; p = 0.001) and p-tau181/Aβ42 (difference of 0.076 per 1-SD change in composite cognition; 95% CI, 0.031–0.122; p = 0.001). These could not be explained by measured biomarkers of non-AD processes, but African Americans may be more susceptible than Caucasians to the cognitive effects of WMH.ConclusionsDespite comparable levels of CSF Aβ42 and Aβ42/Aβ40, cognitive impairment in African Americans is associated with smaller changes in CSF tau markers but greater impact from similar WMH burden than Caucasians. Race-associated differences in CSF tau markers and ratios may lead to underdiagnosis of AD in African Americans.Trial registrationClinicalTrials.gov, NCT02089555. Retrospectively registered on 14 March 2014.
Highlights
African Americans have been reported to have a higher prevalence of Alzheimer’s disease (AD) than Caucasians, but etiology-specific AD biomarkers have not been systematically analyzed in older African Americans
African Americans with AD have greater ischemic and Lewy body copathology and perhaps less transactive response DNA-binding protein 43 kDa (TDP-43) pathology [10, 11]. These findings point to a possible AD endophenotype in African Americans, few epidemiologic or genome-wide association studies have addressed the accuracy of clinical AD diagnosis. This is especially relevant if a greater proportion of African Americans than Caucasians with vascular dementia are misdiagnosed with AD, which can potentially be corrected through antemortem biomarkers associated with amyloid, tau, and vascular pathology
Independent of cognitive functioning, age, sex, apolipoprotein E (APOE) ε4 and ABCA7 risk alleles, and β-Amyloid 1–42 (Aβ42) levels, African Americans had lower levels of t-tau [difference of 23.6 pg/ml; 95% CI, 9.5–37.7; F(2,122) = 10.99; p = 0.001], p-tau181 levels [difference of 7.4 pg/ml; 95% CI, 3.7–11.2 pg/ml; F(2,122) = 15.79; p < 0.001], and β-Amyloid 1–40 (Aβ40) [difference of 1.355 ng/ml; 95% CI, 0.293–2.417 ng/ ml; F(2,122) = 6.385; p = 0.013]
Summary
African Americans have been reported to have a higher prevalence of Alzheimer’s disease (AD) than Caucasians, but etiology-specific AD biomarkers have not been systematically analyzed in older African Americans. African Americans with AD have greater ischemic and Lewy body copathology and perhaps less transactive response DNA-binding protein 43 kDa (TDP-43) pathology [10, 11]. Together, these findings point to a possible AD endophenotype in African Americans, few epidemiologic or genome-wide association studies have addressed the accuracy of clinical AD diagnosis. These findings point to a possible AD endophenotype in African Americans, few epidemiologic or genome-wide association studies have addressed the accuracy of clinical AD diagnosis This is especially relevant if a greater proportion of African Americans than Caucasians with vascular dementia are misdiagnosed with AD, which can potentially be corrected through antemortem biomarkers associated with amyloid, tau, and vascular pathology. African American recruitment into modern AD biomarker studies such as the Alzheimer’s Disease Neuroimaging Initiative (ADNI) has traditionally been limited [12], and there are few longitudinal clinicopathologic studies involving African Americans that have provided autopsy-based information
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