Plasma amyloid β 42/40 ratios as biomarkers for amyloid β cerebral deposition in cognitively normal individuals

Noelia Fandos; Virginia Pérez-Grijalba; Pedro Pesini; Salvador Olmos; Matías Bossa; Victor L Villemagne; James Doecke; Christopher Fowler; Colin L Masters; Manuel Sarasa; AIBL Research Group

doi:10.1016/j.dadm.2017.07.004

Plasma amyloid β 42/40 ratios as biomarkers for amyloid β cerebral deposition in cognitively normal individuals

Alzheimers Dement (Amst). 2017 Sep 12:8:179-187. doi: 10.1016/j.dadm.2017.07.004. eCollection 2017.

Affiliations

¹ R&D Department, Araclon Biotech Ltd., Zaragoza, Spain.
² Aragon Institute of Engineering Research, University of Zaragoza, Zaragoza, Spain.
³ The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia.
⁴ CSIRO Health and Biosecurity/Australian E-Health Research Centre, Brisbane, Queensland, Australia.

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.

Keywords: Amyloid β; Biomarker; Clinical trials; Plasma amyloid β ratio; Positron emission tomography; Preclinical Alzheimer's disease; β-Amyloid imaging.