Head-to-head comparison of amplified plasmonic exosome Aβ42 platform and single-molecule array immunoassay in a memory clinic cohort

Background and purpose: Various blood biomarkers reflecting brain amyloid-beta (A beta) load have recently been proposed with promising results. However, to date, no comparative study amongst blood biomarkers has been reported. Our objective was to examine the diagnostic performance and cost effectiveness of three blood biomarkers on the same cohort. Methods: Using the same cohort (n = 68), the performances of the single-molecule array (Simoa) A beta 40, A beta 42, A beta 42/A beta 40 and the amplified plasmonic exosome (APEX) A beta 42 blood biomarkers were compared using amyloid positron emission tomography (PET) as the reference standard. The extent to which these blood tests can reduce the recruitment cost of clinical trials was also determined by identifying amyloid positive (A beta+) participants. Results:Compared to Simoa biomarkers, APEX-A beta 42 showed significantly higher correlations with amyloid PET retention values and excellent diagnostic performance (sensitivity 100%, specificity 93.3%, area under the curve 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-A beta 42 and 48.6% for Simoa-A beta 42/A beta 40) compared to the situation where only PET imaging is used. Moreover, with 100% sensitivity, APEX-A beta 42 pre-screening does not increase the required number of initial participants. Conclusions: With its high diagnostic performance, APEX is an ideal candidate for A beta+ subject identification, monitoring and primary care screening, and could efficiently enrich clinical trials with A beta+ participants whilst halving recruitment costs.

Automated summary

The study compared three blood biomarkers in terms of diagnostic performance and cost effectiveness, with APEX-A beta 42 showing higher correlation and excellent diagnostic performance. Pre-screening with blood biomarkers can significantly reduce recruitment costs for clinical trials.