Plasma Alzheimer's biomarkers and brain amyloid in Hispanic and non-Hispanic older adults

Abstract

Introduction: Alzheimer's disease studies often lack ethnic diversity.

Methods: We evaluated associations between plasma biomarkers commonly studied in Alzheimer's (p-tau181, GFAP, and NfL), clinical diagnosis (clinically normal, amnestic MCI, amnestic dementia, or non-amnestic MCI/dementia), and Aβ-PET in Hispanic and non-Hispanic older adults. Hispanics were predominantly of Cuban or South American ancestry.

Results: Three-hundred seventy nine participants underwent blood draw (71.9 ± 7.8 years old, 60.2% female, 57% Hispanic of which 88% were Cuban or South American) and 240 completed Aβ-PET. P-tau181 was higher in amnestic MCI (p = 0.004, d = 0.53) and dementia (p < 0.001, d = 0.97) than in clinically normal participants and discriminated Aβ-PET[+] and Aβ-PET[-] (AUC = 0.86). P-tau181 outperformed GFAP and NfL. There were no significant interactions with ethnicity. Among amnestic MCI, Hispanics had lower odds of elevated p-tau181 than non-Hispanic (OR = 0.41, p = 0.006).

Discussion: Plasma p-tau181 informs etiological diagnosis of cognitively impaired Hispanic and non-Hispanic older adults. Hispanic ethnicity may relate to greater likelihood of non-Alzheimer's contributions to memory loss.

Highlights: Alzheimer's biomarkers were measured in Hispanic and non-Hispanic older adults. Plasma p-tau181 related to amnestic cognitive decline and brain amyloid burden. AD biomarker associations did not differ between Hispanic and non-Hispanic ethnicity. Hispanic individuals may be more likely to have non-Alzheimer causes of memory loss.

Keywords: Alzheimer's; GFAP; Hispanic; NfL; amyloid PET; dementia; ethnicity; p-tau181; plasma biomarkers.

FIGURE 1

Plasma biomarker concentration differences between clinical diagnostic groups for p‐tau181, GFAP, and NfL. For p‐tau181, participants diagnosed with AMN‐DEM had significantly higher concentrations than all other groups (black lines), and those with AMN‐MCI had higher concentrations than CN and IMPnonMCI. For both GFAP and NfL, only participants with AMN‐DEM had significantly higher concentrations than other diagnostic groups. Findings did not differ between ethnicity groups. Four participants with very high plasma NfL (> 100 pg/mL, N = 3 AMN‐DEM, N = 1 NONAMN) are not shown visually in the figure to avoid extensive y‐axis distortion. AMN‐DEM, amnestic dementia; AMN‐MCI, amnestic MCI; CN, normal controls; GFAP, glial fibrillary acidic protein; IMPnonMCI, cognitively impaired but not MCI; MCI, mild cognitive impairment; NfL, neurofilament light; NONAMN, non‐amnestic MCI or dementia

FIGURE 2

Association between plasma biomarker concentrations and cortical Aβ burden. Data are shown in relation to a continuous measure of Aβ burden quantified on the Centiloid scale (top row), and between participants classified as having a positive or negative scan (bottom row). For the associations with the Centiloid scale, statistically significant associations were observed in the overall sample (black line) for all biomarkers, but effect sizes were notably larger for plasma p‐tau181 (ρ = 0.59 [0.50 to 0.67]) and GFAP (ρ = 0.42 [0.30 to 0.52]) than for NfL (ρ = 0.23 [0.10 to 0.35]). Results were similar when comparing participants based on dichotomous (positive or negative) Aβ‐PET status. The strength of association between plasma markers and Aβ‐PET outcomes did not significantly differ between Hispanic (orange) and Non‐Hispanic (purple) ethnicity groups. Aβ, beta‐amyloid; GFAP, glial fibrillary acidic protein; NfL, neurofilament light; PET, positron emission tomography

FIGURE 3

Area under the curve analysis demonstrating discriminability between Aβ‐PET positive and negative participants for each plasma biomarker. Data are shown for the overall cohort, Non‐Hispanic participants, and Hispanic participants. Plasma p‐tau181 concentrations most accurately discriminated Aβ‐PET positive and negative participants (maroon) followed by GFAP (blue) and NfL (green). Discrimination accuracy was similar for both ethnicity groups. Aβ, beta‐amyloid; GFAP, glial fibrillary acidic protein; NfL, neurofilament light; PET, positron emission tomography