Total Aβ ₄₂/Aβ ₄₀ ratio in plasma predicts amyloid-PET status, independent of clinical AD diagnosis

Abstract

Objective

To 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.

Methods

Taking plasma samples at 3 separate time points, month 18 (n = 176), month 36 (n = 169), and month 54 (n = 135), we assessed the total Aβ ₄₂/Aβ ₄₀ ratio in plasma (TP42/40) with regard to neocortical Aβ burden via PET standardized uptake value ratio (SUVR) and investigated both association with Aβ-PET status and correlation (and agreement) with SUVR.

Results

The TP42/40 plasma ratio was significantly reduced in amyloid-PET–positive participants at all time points ( p < 0.0001). Adjusting for covariates age, gender, APOE ε4 allele status, and clinical classification clearly affects the significance, with p values reduced and only comparisons at 54 months retaining significance ( p = 0.006). Correlations with SUVR were similar across each time point, with Spearman ρ reaching −0.64 ( p < 0.0001). Area under the curve values were highly reproducible over time points, with values ranging from 0.880 at 36 months to 0.913 at 54 months. In assessments of the healthy control group only, the same relationships were found.

Conclusions

The current study demonstrates reproducibility of the plasma assay to discriminate between amyloid-PET positive and negative over 3 time points, which can help to substantially reducing the screening rate of failure for clinical trials targeting preclinical or prodromal disease.

Classification of evidence

This study provides Class II evidence that plasma total Aβ ₄₂/Aβ ₄₀ ratio is associated with neocortical amyloid burden as measured by PET SUVR.