Association of Plasma and Cerebrospinal Fluid Alzheimer Disease Biomarkers With Race and the Role of Genetic Ancestry, Vascular Comorbidities, and Neighborhood Factors

Abstract

ImportanceDifferences in cerebrospinal fluid (CSF) tau Alzheimer dementia (AD) biomarkers by self-identified race have been observed in prior studies. More recently, plasma biomarkers have been gaining recognition, but whether they exhibit similar differences is unclear. Furthermore, the underlying explanation for these differences in AD biomarkers is still unexplored.ObjectivesTo investigate differences in plasma biomarkers by race and genetic ancestry and explore potential underlying explanations for these differences.Design, Setting, and ParticipantsThis cross-sectional study used participant data from the Brain, Stress, Hypertension, and Aging Research Program (B-SHARP), an observational study conducted in the greater Atlanta metropolitan area. Participants were enrolled from March 1, 2016, to January 1, 2020.Main Outcomes and MeasuresMain outcomes were plasma and CSF amyloid-β (Aβ) 42, Aβ40, phosphorylated tau181 (p-tau181), and neurofilament light. General linear models were used for key comparisons.ExposuresMain independent variables were self-identified race and genetic ancestry. Additional variables were cardiovascular factors, APOE4, educational attainment, Area Deprivation Index, and C-reactive protein (reflecting systemic inflammation state).ResultsThis analysis included 617 participants (mean [SD] age, 66 [7.9] years; 300 [49%] African American and 317 [51%] White; 429 [70%] with mild cognitive impairment). On the basis of self-reported race, plasma levels of Aβ42 (adjusted mean difference, −1.20 pg/mL; 95% CI, −2.33 to −0.07 pg/mL), Aβ40 (adjusted mean difference, −37.78 pg/mL; 95% CI, −60.16 to −15.39 pg/mL), p-tau181 (adjusted mean difference, −4.66 pg/mL; 95% CI, −7.05 to −1.90 pg/mL), and neurofilament light (adjusted mean difference, −1.58; 95% CI, −2.83 to −0.19 pg/mL) were consistently lower in African American individuals after adjusting for demographic characteristics, educational attainment, cognition, APOE4, and cardiovascular factors. A similar pattern was observed in the CSF biomarkers except for Aβ42 and Aβ40. Although unadjusted analyses revealed an association between these biomarkers and African ancestry, these associations were not significant after adjusting for the same covariates. Differences by self-reported race were not explained by varied cardiovascular risk factors, C-reactive protein, educational attainment, or Area Deprivation Index.Conclusions and RelevanceIn this cross-sectional study of plasma biomarkers by race and genetic ancestry, the results indicated that plasma p-tau181, Aβ40, and NFL were lower in African American individuals based on self-reported race but not genetic ancestry. These differences were not explained by cardiovascular risks or clinical stage differences. These racial differences should be considered in clinical interpretations and clinical trial screenings to avoid an additional increase in underrepresentation of African American individuals in AD trials.

Association of Plasma Biomarkers of Alzheimer Disease With Cognition and Medical Comorbidities in a Biracial Cohort

“…9 This study of a large, biracial, community-based sample of adults provides evidence that sex differences and systemic medical comorbidities, but not self-reported race/ethnicity, influence variation in plasma AD biomarkers and therefore need to be accounted for in the development of reference ranges and guidance on clinical interpretation. 10 That study sample consisted predominantly of individuals with MCI and those in a younger age range than ours. In addition, that study did not match on age (AA participants were younger than NHW participants) and did not consider CKD, which is known to elevate plasma biomarker levels.…”

“…A prior study of adults from the greater Atlanta metropolitan area reported lower levels of plasma Aβ 40 , Aβ 42 , p-tau 181 , and NfL in AA individuals compared with those in NHW individuals. 10 That study sample consisted predominantly of individuals with MCI and those in a younger age range than ours. In addition, that study did not match on age (AA participants were younger than NHW participants) and did not consider CKD, which is known to elevate plasma biomarker levels.…”

“…One cross-sectional study of individuals with normal cognition or mild cognitive impairment (MCI) described lower levels of plasma tau phosphorylated at position 181 (p-tau 181 ), β-amyloid (Aβ) peptide 1-42 (Aβ 42 ), and Aβ peptide 1-40 (Aβ 40 ) in African American (AA) individuals compared with those in non-Hispanic White (NHW) individuals. 10 A different study reported lower plasma Aβ 40 and higher total tau in cognitively normal Mexican American individuals compared with those in NHW individuals. 11 However, no plasma biomarker differences (total tau, p-tau 181 , p-tau 217 , Aβ 42 /Aβ 40 , and neurofilament light [NfL]) by self-reported race were observed in analyses of a separate multiethnic, community-based cohort.…”

Design and feasibility of an Alzheimer’s disease blood test study in a diverse community-based population

“…Minoritized groups have a higher risk of AD dementia [18][19][20], making it especially problematic that they are underrepresented in AD research [21]. Several studies have found racial differences in AD biomarkers, including lower average CSF total tau and p-tau181 concentrations in Black or African American compared to non-Hispanic White participants [22][23][24][25]. Although AD blood tests may perform differently across racial groups in predicting AD pathology [25], this is difficult to clearly establish because so few individuals from minoritized groups have samples available for analysis [26,27].…”

Design and feasibility of an Alzheimer's disease blood test study in a diverse community‐based population

“…Minoritized groups have a higher risk of AD dementia, 18–20 making it especially problematic that they are underrepresented in AD research 21 . Several studies have found racial differences in AD biomarkers, including lower average CSF total tau and p‐tau181 concentrations in Black or African American compared to non‐Hispanic White participants 22–25 . Although AD blood tests may perform differently across racial groups in predicting AD pathology, 25 this is difficult to clearly establish because so few individuals from minoritized groups have samples available for analysis 26,27 .…”