Characterization of plasma AT(N) biomarkers among a racial and ethnically diverse community-based cohort: an HABS-HD study

Abstract

Introduction: Alzheimer's disease (AD) biomarkers of Amyloid(A), Tau(T), and Neurodegeneration(N) have been increasingly studied to fill the gap in our understanding of racial and ethnic differences. This study aimed to examine the relationship between plasma AT(N) biomarkers and (1) AT(N) neuroimaging biomarkers, (2) demographics, (3) medical comorbidities, and (4) cognitive diagnosis.

Methods: Data were analyzed from n = 764 non-Hispanic Black (NHB), n = 1230 Hispanic, and n = 1232 non-Hispanic White (NHW) participants. Plasma AT(N) biomarkers were derived using single molecule array (SIMOA) technology on an HD-X imager and included amyloid beta (Aβ)42/40, total tau, ptau181, and neurofilament light chain (NfL). Clinical reads of positron emission tomography (PET) amyloid and tau positivity were used to examine the link between AT(N) plasma and neuroimaging biomarkers. Generalized linear models were conducted to examine the relationship between plasma AT(N) biomarkers and select demographic, diagnostic, and medical comorbidities (hypertension, diabetes, dyslipidemia, chronic kidney disease).

Results: Differences in the AT(N) biomarkers were found across racial/ethnic groups. Plasma Aβ42/40 was found to be associated with PET amyloid positivity only among NHW participants, while plasma NfL was found to correlate with Meta-ROI among NHB and Hispanic participants. Ptau181 was associated with PET amyloid positivity among NHB and NHW participants and well as PET tau positivity among the latter group and Hispanic participants. Diabetes was related to increased plasma AT(N) biomarkers among NHB and Hispanic participants. CKD was associated with increased AT(N) biomarkers for all race/ethnic groups with the exception of Aβ42/40. While Aβ42/40, total tau, ptau181, and NfL were found to be related to a dementia diagnosis among NHW participants, only ptau181 and NfL were found to be related to this same diagnostic category among NHB and Hispanic participants.

Discussion: Our findings indicate differential relationships between comorbidities (demographic, medical, diagnostic) across NHB, Hispanic, and NHW participants. This work expands our knowledge regarding the associations of plasma biomarkers to AD pathology in diverse populations.

Highlights: Differences in AT(N) plasma biomarkers were found in a diverse community cohort.While plasma Aβ42/40 was associated with PET amyloid positivity among non-Hispanic white participants, this did not apply to non-Hispanic Black or Hispanic participants.Medical comorbidity of diabetes and chronic kidney disease was related to increased plasma AT(N) biomarkers among the ethnically diverse segment of the cohort.Plasma AT(N) biomarkers were more so related to a diagnosis of dementia for non-Hispanic white as compared to Hispanic or non-Hispanic Black participants.Across racial/ethnic groups, the plasma biomarkers of neurodegeneration (NfL) and ptau181 were related to a diagnosis of dementia.

Keywords: AT(N); Black participants; Hispanic participants; biomarkers; community‐based; plasma.

FIGURE 1

Violin plot for amyloid beta (Aβ) 42/40 ratio levels by race/ethnic group based on a positron emission tomography amyloid positivity status.

FIGURE 2

Boxplots for plasma AT(N) biomarker levels (adjusted by age, gender, and education) stratified by (A) amyloid beta (Aβ) 42/40 ratio, (B) total Tau, (C) pTau181, and (D) neurofilament light chain (NfL) as well as by race/ethnic group and cognitive diagnosis. Significance p < 0.05*, p < 0.01**, p < 0.001***, p < 0.0001****. CU, cognitively unimpaired; MCI, mild cognitive impairment.