Plasma amyloid beta biomarkers predict amyloid positivity and longitudinal clinical progression in mild cognitive impairment

INTRODUCTION Previous studies have examined the predictive accuracy of plasma amyloid beta (A beta) biomarkers in clinical cohorts. However, their accuracy for predicting amyloid-positive patients in community-based cohorts is unclear. This study aimed to determine the predictive accuracy of A beta precursor protein 669-711/A beta 1-42, A beta 1-40/1-42 and their composite biomarkers for brain amyloid deposition or the clinical progression in community-dwelling older adults with mild cognitive impairment (MCI). METHODS This prospective cohort study was conducted from August 2015 to September 2019. Subsequently, the participants underwent follow-up cognitive assessments up to 8 years after the start of the study. Blood samples were collected from older adults aged >= 65 years with MCI at baseline. Plasma A beta biomarkers were analyzed using immunoprecipitation-mass spectrometry. The accuracy of plasma biomarkers for brain amyloid status was evaluated using receiver operating characteristic curve analysis. Relationships between comorbidities and plasma A beta markers were examined using multiple linear regression analysis. Associations of plasma biomarkers with clinical conversion to Alzheimer's disease (AD) dementia were evaluated using Kaplan-Meier curves. RESULTS The participants included 107 patients (57 [53.3%] females, median age: 76.0 [72.0-80.0] years). Plasma biomarkers correlated with cortical amyloid uptake (rho = 0.667-0.754). The composite biomarker had the best area under the curve (0.943, 95% confidence interval [CI]: 0.901 to 0.985) for predicting amyloid positivity. Apolipoprotein epsilon 4 status showed significant correlations with increased plasma amyloid biomarker levels. Participants with high composite biomarker levels at baseline had a greater risk of conversion to AD dementia (hazard ratio 10.74, 95% CI: 3.51 to 32.84, P < 0.001). The higher composite biomarker was associated with a faster rate of cognitive decline (rho = -0.575, P < 0.001). DISCUSSION Plasma A beta composite biomarker may serve as a surrogate measure for amyloid deposition and a predictor of disease progression in a community-based cohort.