Plasma amyloid β 42/40 ratios as biomarkers for amyloid β cerebral deposition in cognitively normal individuals. Issue 1 (30th August 2017)

• Record Type: Journal Article
• Authors: Fandos, Noelia; Pérez‐Grijalba, Virginia; Pesini, Pedro; Olmos, Salvador; Bossa, Matías; Villemagne, Victor L.; Doecke, James; Fowler, Christopher; Masters, Colin L.; Sarasa, Manuel
• Is Part Of: Alzheimer's & dementia. Volume 8:Issue 1(2017)
• Page Start: 179
• Page End: 187
• Publication Date: 2017-08-30
• Subjects: Amyloid β -- Plasma amyloid β ratio -- Biomarker -- Preclinical Alzheimer's disease -- β‐Amyloid imaging -- Positron emission tomography -- Clinical trials; Alzheimer's disease -- Periodicals; Alzheimer's disease -- Diagnosis -- Periodicals; Dementia -- Periodicals; Dementia -- Diagnosis -- Periodicals; 616.831
• DOI: 10.1016/j.dadm.2017.07.004
• Languages: English
• ISSNs: 2352-8729

Abstract

Abstract: Introduction: Plasma amyloid β (Aβ) peptides have been previously studied as candidate biomarkers to increase recruitment efficiency in secondary prevention clinical trials for Alzheimer's disease. Methods: Free and total Aβ42/40 plasma ratios (FP42/40 and TP42/40, respectively) were determined using ABtest assays in cognitively normal subjects from the Australian Imaging, Biomarker and Lifestyle Flagship Study. This population was followed‐up for 72 months and their cortical Aβ burden was assessed with positron emission tomography. Results: Cross‐sectional and longitudinal analyses showed an inverse association of Aβ42/40 plasma ratios and cortical Aβ burden. Optimized as a screening tool, TP42/40 reached 81% positive predictive value of high cortical Aβ burden, which represents 110% increase over the population prevalence of cortical Aβ positivity. Discussion: These findings support the use of plasma Aβ42/40 ratios as surrogate biomarkers of cortical Aβ deposition and enrichment tools, reducing the number of subjects submitted to invasive tests and, consequently, recruitment costs in clinical trials targeting cognitively normal individuals. Highlights: Association of plasma Aβ42/40 ratios was assessed in cognitively normal subjects. Low plasma Aβ42/40 ratios are associated with high Aβ deposition in brain. Prediction of preclinical cortical Aβ burden can be improved using plasma Aβ42/40. Enrichment strategies using plasma Aβ42/40 could lead to economical savings. Plasma Aβ42/40 biomarkers could become cost‐effective tools for preclinical recruitment.