Risk of Alzheimer's disease is associated with longitudinal changes in plasma biomarkers in the multi-ethnic Washington Heights-Hamilton Heights-Inwood Columbia Aging Project (WHICAP) cohort.

ABSTRACT

BACKGROUND: Alzheimer's disease (AD) biomarkers can help differentiate cognitively unimpaired (CU) individuals from mild cognitive impairment (MCI) and dementia. The role of AD biomarkers in predicting cognitive impairment and AD needs examination. METHODS: In 628 CU individuals from a multi-ethnic cohort, amyloid beta (Aß)42, Aß40, phosphorylated tau-181 (p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) were measured in plasma. RESULTS: Higher baseline levels of p-tau181/Aß42 ratio were associated with an increased risk of incident dementia. A biomarker pattern (with elevated Aß42/Aß40 but low p-tau181/Aß42) was associated with decreased dementia risk. Compared to CU, participants who developed MCI or dementia had a rapid decrease in this protective biomarker pattern reflecting AD-specific pathological change. DISCUSSION: Elevated levels of AD biomarker p-tau181/Aß42, by itself or combined with a low Aß42/Aß40 level, predicts clinically diagnosed AD. Individuals with a rapid change in these biomarkers may need close monitoring for the potential downward trajectory of cognition. HIGHLIGHTS We discuss a multi-ethnic, urban community study of elderly individuals. The study consisted of a longitudinal assessment over 6 years with repeated clinical assessments. The study used blood-based biomarkers as predictors of mild cognitive impairment and Alzheimer's disease.