European Journal of Neurology | December 28, 2020

Tanaka T, Ruifen JC, Ying-Hwey N, Tan CH, Lim CZJ, Zhang Y, Stephenson MC, Hilal S, Saridin FN, Gyanwali B, Villaraza S, Robins EG, Ihara M, Schöll M, Zetterberg H, Blennow K, Ashton NJ, Shao H, Reilhac A and Chen C

Eur J Neurol. 2020 Dec 28

DOI: https://doi.org/10.1111/ene.14704

Abstract

Background

Various blood biomarkers reflecting brain amyloid‐β (Aβ) load have recently been proposed with promising results. However, to date, no comparative study among blood biomarkers has been reported. Our objective is to examine the diagnostic performance and cost effectiveness of three blood biomarkers on the same cohort.

Methods

Using the same cohort (n=68), we compared the performance of the single‐molecule array (Simoa)‐Aβ40 and Aβ42, Aβ42/Aβ40 and the amplified plasmonic exosome (APEX)‐Aβ42 blood biomarkers using amyloid PET as the reference standard. We also determined the extent to which these blood tests can reduce the recruitment cost of clinical trials by identifying Amyloid positive (Aβ+) participants.

Results

Compared to Simoa biomarkers, APEX‐Aβ42 showed significantly higher correlations with amyloid PET retention values and excellent diagnostic performance (sensitivity=100%, specificity=93.3%, AUC=0.995). When utilized for clinical trial recruitment, our simulation showed that pre‐screening with blood biomarkers followed by a confirmatory amyloid PET imaging would roughly half the cost (56.8% reduction for APEX‐Aβ42 and 48.6% for Simoa‐Aβ42/Aβ40) as compared to the situation where only PET imaging is used. Moreover, with a 100% sensitivity; APEX‐Aβ42 pre‐screening does not increase the required number of initial participants.

Conclusions

With its high diagnostic performance, APEX is an ideal candidate for Aβ+ subject identification, monitoring, primary care screening, and could efficiently enrich clinical trials with Aβ+ participants while halving recruitment costs.