Plasma biomarkers of Alzheimer's disease and related dementias in American Indians: The Strong Heart Study.

ABSTRACT

INTRODUCTION: Identification of Alzheimer's disease (AD) needs inexpensive, noninvasive biomarkers, with validation in all populations. METHODS: We collected plasma markers in older American Indian individuals phosphorylated-tau181 (pTau181); amyloid-beta (Aß) 40,42; glial fibrillary acidic protein (GFAP); and neurofilament light chain (NfL). Plasma markers were analyzed for discriminant properties with cognitive status and etiology using receiver operating characteristic (ROC) analysis. RESULTS: PTau181, GFAP, NfL plasma values were significantly associated with cognition, but Aß were not. Discriminant performance was moderate for individual markers, with pTau181, GFAP, NfL performing best, but an empirically selected panel of markers (age, sex, education, pTau181, GFAP, NfL, Aß4240 ratio) had excellent discriminant performance (AUC > 0.8). DISCUSSION: In American Indian individuals, pTau181 and Aß values suggested more common pathology than in majority populations. Aß was less informative than in other populations; however, all four markers were needed for a best-performing dementia diagnostic model. These data validate utility of AD plasma markers, while suggesting population-specific diagnostic characteristics.