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

Abstract

Background and Objectives:Recent advances in blood-based biomarkers offer the potential to revolutionize diagnosis and management of Alzheimer’s disease (AD), but additional research in diverse populations is critical. We assessed the profiles of blood-based AD biomarkers and their relationships to cognition and common medical comorbidities in a biracial cohort.Methods:Participants were evaluated through the Mayo Clinic Jacksonville Alzheimer’s Disease Research Center and matched on age, sex, and cognitive status. Plasma AD biomarkers (Aβ42/40, p-tau181, GFAP, NfL) were measured using the Quanterix SiMoA HD-X analyzer. Cognition was assessed with the Mini Mental State Examination. Wilcoxon rank sum tests were used to assess for differences in plasma biomarker levels by sex. Linear models tested for associations of self-reported race, chronic kidney disease (CKD), and vascular risk factors with plasma AD biomarker levels. Additional models assessed for interactions between race and plasma biomarkers in predicting cognition.Results:The sample comprised African-American (AA; N=267) and non-Hispanic White (NHW; N=268) participants, including 69% female participants and age range 43-100 (median 80.2) years. Education was higher in NHW participants (median 16 vs. 12 years,p<0.001) whileAPOE(apolipoprotein E) ε4 positivity was higher in AA participants (43% vs. 34%;p=0.04). We observed no differences in plasma AD biomarker levels between AA and NHW participants. These results were unchanged after stratifying by cognitive status (unimpaired versus impaired). Although the p-tau181-cognition association appeared stronger in NHW participants while the Aβ42/40-cognition association appeared stronger in AA participants, these findings did not survive after excluding individuals with CKD. Female participants displayed higher GFAP (177.5 pg/ml vs. 157.73 pg/ml;p=0.002) and lower p-tau181(2.62 pg/ml vs. 3.28 pg/ml;p=0.001) levels than male participants. Diabetes was inversely associated with GFAP levels (β=-0.01;p<0.001).Discussion:In a biracial, community-based sample of adults, we observed that sex differences, CKD, and vascular risk factors, but not self-reported race, contributed to variation in plasma AD biomarkers. Although some prior studies have reported primary effects of race/ethnicity, our results reinforce the need to account for broad-based medical and social determinants of health (including sex, systemic comorbidities, and other factors) in effectively and equitably deploying plasma AD biomarkers in the general population.

The Relationship of Cerebrospinal Fluid Biomarkers and Cognitive Performance in Frontotemporal Dementia

“…On the other hand, our ndings in AD patients align with prior research, indicating a stronger correlation between cognitive measures and tau markers when compared to Aβ1-42 in AD 28, 29 . In a recent study by Ramanan et al 2023 involving a large cohort of patients with AD, no association was found between the Aβ 42/40 ratio and MMSE scores in the overall sample, whereas p-tau 181 levels exhibited a positive association with MMSE scores 30 . The lack of signi cant ndings in our study and previous studies related to Aβ1-42 levels and cognition in patients with AD can be attributed to a hypothesis proposing that amyloid load remains relatively stable in the brain throughout various clinical phases of AD and does not exhibit substantial changes as the disease progresses to more severe stages 31 .…”

The Relationship of Cerebrospinal Fluid Biomarkers and Cognitive Performance in Frontotemporal Dementia

“…On the other hand, our ndings in AD patients align with prior research, indicating a stronger correlation between cognitive measures and tau markers when compared to Aβ1-42 in AD 28,29 . In a recent study by Ramanan et al 2023 involving a large cohort of patients with AD, no association was found between the Aβ 42/40 ratio and MMSE scores in the overall sample, whereas p-tau 181 levels exhibited a positive association with MMSE scores 30 . The lack of signi cant ndings in our study and previous studies related to Aβ1-42 levels and cognition in patients with AD can be attributed to a hypothesis proposing that amyloid load remains relatively stable in the brain throughout various clinical phases of AD and does not exhibit substantial changes as the disease progresses to more severe stages 31 .…”

Performance of the Lumipulse plasma Aβ42/40 and pTau181 immunoassays in the detection of amyloid pathology

“…Also, participants of this community‐based cohort were predominantly white. Prior studies examining performance of BBBs in racial and ethnic diverse groups have been conflicting 31 , 32 , 33 , 34 and more data are needed to determine if the diagnostic performance observed in this study is applicable to more diverse populations. Finally, we used amyloid‐PET as the outcome measure; therefore, studies examining performance of BBBs using CSF biomarkers to characterize amyloid pathology may not be directly comparable as CSF markers can also have varying performance for detecting an abnormal amyloid‐PET.…”