2 research outputs found
Plasma Aβ42/40 ratio alone or combined with FDG-PET can accurately predict amyloid-PET positivity: a cross-sectional analysis from the AB255 Study
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 (Aβ) levels with the presence of pathological accumulation of Aβ in the brain measured by
amyloid-PET. Both plasma Aβ42/40 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 Aβ40 and Aβ42 levels in plasma (TP42/40) were quantified
using ABtest kits. Subjects were dichotomized as Aβ-PET positive or negative, and the ability of TP42/40 to detect
Aβ-PET positivity was assessed by logistic regression and receiver operating characteristic analyses. Combination of
plasma Aβ biomarkers and FDG-PET was further assessed as an improvement for brain amyloidosis detection and
diagnosis classification.
Results: Eighteen (30.5%) subjects were Aβ-PET positive. TP42/40 ratio alone identified Aβ-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 Aβ-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 Aβ-PET scans by 64%. Combination of both FDG-PET
scores and plasma Aβ biomarkers was found to be the most accurate Aβ-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
Aβ positivity in preclinical and prodromal stages of Alzheimer’s disease
Plasma Aβ42/40 ratio alone or combined with FDG-PET can accurately predict amyloid-PET positivity: a cross-sectional analysis from the AB255 Study
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 (Aβ) levels with the presence of pathological accumulation of Aβ in the brain measured by
amyloid-PET. Both plasma Aβ42/40 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 Aβ40 and Aβ42 levels in plasma (TP42/40) were quantified
using ABtest kits. Subjects were dichotomized as Aβ-PET positive or negative, and the ability of TP42/40 to detect
Aβ-PET positivity was assessed by logistic regression and receiver operating characteristic analyses. Combination of
plasma Aβ biomarkers and FDG-PET was further assessed as an improvement for brain amyloidosis detection and
diagnosis classification.
Results: Eighteen (30.5%) subjects were Aβ-PET positive. TP42/40 ratio alone identified Aβ-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 Aβ-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 Aβ-PET scans by 64%. Combination of both FDG-PET
scores and plasma Aβ biomarkers was found to be the most accurate Aβ-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
Aβ positivity in preclinical and prodromal stages of Alzheimer’s disease