IntroductionPlasma amyloid β (Aβ) peptides have been previously studied as candidate biomarkers to increase recruitment efficiency in secondary prevention clinical trials for Alzheimer's disease.MethodsFree 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.ResultsCross-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.DiscussionThese 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.

Introduction: Pre-analytical sample handling might affect the results of Alzheimer's disease blood-based biomarkers. We empirically tested variations of common blood collection and handling procedures. Methods:We created sample sets that address the effect of blood collection tube type, and of ethylene diamine tetraacetic acid plasma delayed centrifugation, centrifugation temperature, aliquot volume, delayed storage, and freeze-thawing. We measuredThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

ObjectiveTo explore whether the plasma total β-amyloid (Aβ) Aβ 42 /Aβ 40 ratio is a reliable predictor of the amyloid-PET status by exploring the association between these 2 variables in a subset of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging cohort.

Introduction We investigated the relationship of plasma amyloid beta (Aβ) with cerebral deposition of Aβ and tau on positron emission tomography (PET). Methods Forty-four participants (18 cognitively normal older adults [CN], 10 mild cognitive impairment, 16 Alzheimer's disease [AD]) underwent amyloid PET and a blood draw. Free and total plasma Aβ40 and Aβ42 were assessed using a validated assay. Thirty-seven participants (17 CN, 8 mild cognitive impairment, 12 AD) also underwent a [ 18 F]flortaucipir scan. Scans were preprocessed by standard techniques, and mean global and regional amyloid and tau values were extracted. Free Aβ42/Aβ40 (Aβ F42:F40) and total Aβ42/Aβ40 (Aβ T42:T40) were evaluated for differences by diagnosis and relation to PET Aβ positivity. Relationships between these measures and cerebral Aβ and tau on both regional and voxel-wise basis were also evaluated. Results Lower Aβ T42:T40 was associated with diagnosis and PET Aβ positivity. Lower plasma Aβ T42:T40 ratios predicted cerebral Aβ positivity, both across the full sample and in CN only. Finally, lower plasma Aβ T42:T40 ratios were associated with increased cortical Aβ and tau in AD-related regions on both regional and voxel-wise analyses. Discussion Plasma Aβ measures may be useful biomarkers for predicting cerebral Aβ and tau. Additional studies in larger samples are warranted.

Plasma amyloid-β peptide concentration has recently been shown to have high accuracy to predict amyloid-β plaque burden in the brain. These amyloid-β plasma markers will allow wider screening of the population and simplify and reduce screening costs for therapeutic trials in Alzheimer’s disease. The aim of this study was to determine how longitudinal changes in blood amyloid-β track with changes in brain amyloid-β. Australian Imaging, Biomarker and Lifestyle study participants with a minimum of two assessments were evaluated (111 cognitively normal, 7 mild cognitively impaired, 15 participants with Alzheimer’s disease). Amyloid-β burden in the brain was evaluated through PET and was expressed in Centiloids. Total protein amyloid-β 42/40 plasma ratios were determined using ABtest® assays. We applied our method for obtaining natural history trajectories from short term data to measures of total protein amyloid-β 42/40 plasma ratios and PET amyloid-β. The natural history trajectory of total protein amyloid-β 42/40 plasma ratios appears to approximately mirror that of PET amyloid-β, with both spanning decades. Rates of change of 7.9% and 8.8%, were observed for total protein amyloid-β 42/40 plasma ratios and PET amyloid-β, respectively. The trajectory of plasma amyloid-β preceded that of brain amyloid-β by a median value of 6 years (significant at 88% confidence interval). These findings, showing the tight association between changes in plasma and brain amyloid-β, support the use of plasma total protein amyloid-β 42/40 plasma ratios as a surrogate marker of brain amyloid-β. Also, that plasma total protein amyloid-β 42/40 plasma ratios has potential utility in monitoring trial participants, and as an outcome measure.