Plasma Aß42/40 ratio alone or combined with FDG-PET can accurately predict amyloid-PET positivity: a cross-sectional analysis from the AB255 Study

Abstract

BACKGROUND: To facilitate population screening and clinical trials of disease-modifying therapies for Alzheimer's disease, supportive biomarker information is necessary. This study was aimed to investigate the association of plasma amyloid-beta (A?) levels with the presence of pathological accumulation of A? in the brain measured by amyloid-PET. Both plasma A?42/40 ratio alone or combined with an FDG-PET-based biomarker of neurodegeneration were assessed as potential AD biomarkers. METHODS: We included 39 cognitively normal subjects and 20 patients with mild cognitive impairment from the AB255 Study who had undergone PiB-PET scans. Total A?40 and A?42 levels in plasma (TP42/40) were quantified using ABtest kits. Subjects were dichotomized as A?-PET positive or negative, and the ability of TP42/40 to detect A?-PET positivity was assessed by logistic regression and receiver operating characteristic analyses. Combination of plasma A? biomarkers and FDG-PET was further assessed as an improvement for brain amyloidosis detection and diagnosis classification. RESULTS: Eighteen (30.5%) subjects were A?-PET positive. TP42/40 ratio alone identified A?-PET status with an area under the curve (AUC) of 0.881 (95% confidence interval [CI] = 0.779-0.982). Discriminating performance of TP42/40 to detect A?-PET-positive subjects yielded sensitivity and specificity values at Youden's cutoff of 77.8% and 87.5%, respectively, with a positive predictive value of 0.732 and negative predictive value of 0.900. All these parameters improved after adjusting the model for significant covariates. Applying TP42/40 as the first screening tool in a sequential diagnostic work-up would reduce the number of A?-PET scans by 64%. Combination of both FDG-PET scores and plasma A? biomarkers was found to be the most accurate A?-PET predictor, with an AUC of 0.965 (95% CI = 0.913-0.100). CONCLUSIONS: Plasma TP42/40 ratio showed a relevant and significant potential as a screening tool to identify brain A? positivity in preclinical and prodromal stages of Alzheimer's disease.