• Media type: E-Article
  • Title: Plasma Aβ42/40 ratio alone or combined with FDG-PET can accurately predict amyloid-PET positivity: a cross-sectional analysis from the AB255 Study
  • Contributor: Pérez-Grijalba, Virginia; Arbizu, Javier; Romero, Judith; Prieto, Elena; Pesini, Pedro; Sarasa, Leticia; Guillen, Fernando; Monleón, Inmaculada; San-José, Itziar; Martínez-Lage, Pablo; Munuera, Josep; Hernández, Isabel; Buendía, Mar; Sotolongo-Grau, Oscar; Alegret, Montserrat; Ruiz, Agustín; Tárraga, Lluis; Boada, Mercè; Sarasa, Manuel
  • imprint: Springer Science and Business Media LLC, 2019
  • Published in: Alzheimer's Research & Therapy
  • Language: English
  • DOI: 10.1186/s13195-019-0549-1
  • ISSN: 1758-9193
  • Keywords: Cognitive Neuroscience ; Neurology (clinical) ; Neurology
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>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.</jats:p></jats:sec>
  • Access State: Open Access