Plasma amyloid-β biomarkers for predicting amyloid positivity in mild cognitive impairment: a prospective cohort study

Abstract Background: This study aimed to determine the predictive accuracy of amyloid-β precursor protein 669-711/amyloid-β1-42, amyloid-β1-40/1-42, and their composite biomarkers for brain amyloid deposition or the development of Alzheimer’s disease (AD) dementia in community-dwelling older adults with mild cognitive impairment(MCI). Methods: This was a prospective cohort study conducted from August 2015 to September 2019. Blood samples were collected from older adults aged ≥65 years with MCI without dementia at baseline. Cognitive function and amyloid deposition were evaluated annually. Positron emission tomography was used to evaluate amyloid deposition. Plasma amyloid-β biomarkers were analyzed using immunoprecipitation-mass spectrometry. The classification accuracy of plasma biomarkers for brain amyloid status was evaluated using receiver operating characteristic curve analysis. Associations of plasma biomarkers with clinical conversion to AD dementia were evaluated using Kaplan‒Meier curves. Associations of plasma biomarkers with body mass index, apolipoprotein E4 status, cortical amyloid uptake, medical history, and hepatic or renal dysfunction were examined using multiple linear regression analysis. Results: The participants included 107 patients (57 [53.3%] females, median age: 76.00 [72.00–80.00] years). Plasma biomarkers correlated with cortical amyloid uptake. The composite biomarker had the best area under the curve (0.943) for predicting amyloid positivity. Participants with high levels of composite biomarkers at baseline had a greater rate of conversion to AD dementia. Apolipoprotein E4 status and hepatic disorders were significantly correlated with increased plasma amyloid biomarker levels. Conclusions: Composite amyloid biomarkers may serve as a surrogate measure for amyloid deposition in a community-based cohort. Trial Registration: UMIN000017442