Comparison of a multi‐analyte algorithmic immunoassay blood test with immunoprecipitation mass spectrometry for the detection of amyloid pathology

INTRODUCTION Alzheimer's blood‐based biomarker (BBM) tests using single biomarkers or ratios are well characterized, but head‐to‐head comparisons of multi‐analyte algorithmic tests on shared cohorts are lacking. We compared a five‐biomarker algorithmic immunoassay (LucentAD Complete) with an algorithmic immunoprecipitation mass‐spectrometry (IP‐MS) benchmark on a shared plasma cohort. METHODS Symptomatic individuals ( n = 192) with longitudinal samples from Alzheimer's Disease Neuroimaging Initiative (ADNI) were analyzed versus amyloid positron emission tomography (PET). Cross‐sectional ( n = 115) and longitudinal ( n = 179; 12‐year span) cohorts representing disease progression were used. RESULTS The immunoassay amyloid risk score demonstrated a 0.94 area under the curve (AUC) and 92%–93% accuracy, achieving performance parity with IP‐MS metrics on shared samples. The two‐cutoff design yielded an intermediate zone of 10.4%–12.8%. DISCUSSION These results establish diagnostic parity between algorithmic immunoassay and algorithmic IP‐MS assay. In addition, providing individual biomarker results alongside a validated risk score offers a more granular foundation for comprehensive management than amyloid status alone, supporting premium reimbursement for multi‐analyte algorithmic BBMs in clinical practice.