Plasma A beta 42/40 ratio alone or combined with FDG-PET can accurately predict amyloid-PET positivity: a cross-sectional analysis from the AB255 Study

Autor: Perez-Grijalba, V, Arbizu, J, Romero, J, Prieto, E, Pesini, P, Sarasa, L, Guillen, F, Monleon, I, San-Jose, I, Martinez-Lage, P, Munuera, J, Hernandez, I, Buendia, M, Sotolongo-Grau, O, Alegret, M, Ruiz, A, Tarraga, L, Boada, M, Sarasa, M, Goni, M, Pujadas, F, Villarejo, A, Frank, A, Pena-Casanova, J, Fernandez, M, Pinol, G, Blesa, R, Gil, P, Pascual, LF, Aguilar, M, Frisoni, GB, Matias-Guiu, J, Andreasen, N, Antunez, C
Rok vydání: 2019
Předmět:
Zdroj: Alzheimers Research & Therapy
r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname
ISSN: 1758-9193
Popis: 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 beta) levels with the presence of pathological accumulation of A beta in the brain measured by amyloid-PET. Both plasma A beta 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 beta 40 and A beta 42 levels in plasma (TP42/40) were quantified using ABtest kits. Subjects were dichotomized as A beta-PET positive or negative, and the ability of TP42/40 to detect A beta-PET positivity was assessed by logistic regression and receiver operating characteristic analyses. Combination of plasma A beta biomarkers and FDG-PET was further assessed as an improvement for brain amyloidosis detection and diagnosis classification. Results Eighteen (30.5%) subjects were A beta-PET positive. TP42/40 ratio alone identified A beta-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 beta-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 beta-PET scans by 64%. Combination of both FDG-PET scores and plasma A beta biomarkers was found to be the most accurate A beta-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 beta positivity in preclinical and prodromal stages of Alzheimer's disease.
Databáze: OpenAIRE
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