Developing Topics.

BACKGROUND

A previous comparative analysis of plasma Aβ42/40 immunoassays and mass spectrometry-based assays conducted in 2021 found that several assays had strong performance in predicting amyloid PET status (Zicha et al., 2022). In the spirit of enabling the National Institute on Aging and the Alzheimer's Association framework for classifying Alzheimer's disease (AD) utilizing measures of pathology for amyloid, tau, and neurodegeneration (ATN), we have added to this comparative analysis a newly developed immunoassay on an automated, scalable platform. Robustly validated plasma Aβ assays represent a non-invasive and cost-effective alternative to CSF or neuroimaging for early detection of Alzheimer's disease pathology and screening participants for enrollment into clinical trials.

METHOD

The project team consists of pharmaceutical industry, patient advocacy, governmental, and academic representatives. The current study utilized an additional aliquot of the same 130 plasma samples provided by ADNI that were previously tested on three immunoassays and three mass spectrometry-based assays. The statistical analysis plan was performed as published previously to determine if the measurement of plasma Aβ with age and APOE ε4 status performs better than age and APOE ε4 status alone in determining amyloid PET status.

RESULT

In this sample cohort, the new automated immunoassay with age and APOE genotype had similar prediction of amyloid status compared to mass spectrometry-based assays, with an ROC AUC of 85.7 (95% CI: 79.1 - 92.4) for the immunoassay and 84.2 (95% CI: 77.0 - 91.3) for the best- performing mass spectrometry-based assay. The Spearman correlation of plasma Aβ42/40 with amyloid PET (florbetapir standardized uptake value ratio) for the new immunoassay was -0.567 (p < 0.001) compared to -0.536 (p < 0.001) for the best performing mass spectrometry-based assay. The new immunoassay significantly improved the prediction of amyloid positivity beyond age and APOE ε4 genotype (p = 0.003).

CONCLUSION

Results from this comparative analysis together with the continued advancement in plasma assay technology identify a potential use for plasma Aβ42/40 measurement in addressing the amyloid component of the ATN framework. Further evaluation of plasma Aβ42/40 in addition to p-tau in plasma is planned using longitudinal samples to determine the ability of plasma biomarkers to detect amyloidosis.

Informations de copyright

© 2023 the Alzheimer's Association.