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

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 (A beta)42, A beta 40, 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/A beta 42 ratio were associated with an increased risk of incident dementia. A biomarker pattern (with elevated A beta 42/A beta 40 but low p-tau181/A beta 42) 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/A beta 42, by itself or combined with a low A beta 42/A beta 40 level, predicts clinically diagnosed AD. Individuals with a rapid change in these biomarkers may need close monitoring for the potential downward trajectory of cognition.