Risk of Alzheimer's Disease is Associated with Longitudinal Changes in Plasma Biomarkers in the Multiethnic Washington Heights, Inwood Columbia Aging Project Cohort

INTRODUCTIONAlzheimers 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. METHODSIn 628 CU individuals from a multi-ethnic cohort, A{beta}42, A{beta}40, phosphorylated tau-181 (P-tau181), glial fibrillary acid protein (GFAP), and neurofilament light chain (NfL) were measured in plasma. RESULTSHigher baseline levels of P-tau181/A{beta}42 ratio were associated with 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 the biomarker pattern reflecting AD-specific pathological change. DISCUSSIONElevated 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. Research in ContextO_LISystematic Review: Few studies have evaluated the clinical application of AD blood-based biomarkers longitudinally as antecedent risk predictors. Data from multiethnic populations are even more limited. How preclinical trajectories of blood-based biomarkers are related with the risk of developing clinically diagnosed MCI or AD is largely unknown. C_LIO_LIInterpretation: High circulating level of P-tau181/A{beta}42, by itself or combined with a low level of A{beta}42/A{beta}40, may predict development of incident clinical AD. Biomarkers levels of P-tau181, P-tau181/A{beta}42, and NfL increase with age even among individuals who remain cognitively healthy. A rapid change in biomarkers may indicate the individuals in the active trajectory to develop clinically diagnosed MCI or AD. C_LIO_LIFuture Directions: Larger studies or meta-analyses are needed to examine whether the predictive utility of blood-based biomarkers for AD differs across racial/ethnic groups. Well-designed studies are needed to evaluate the optimal duration between repeated measures of biomarkers. C_LI