Diagnostic Performance and Clinical Utility of Automated Plasma Amyloid-β 1-42/1-40 Assay

Background: Blood-based biomarkers offer an accessible alternative to cerebrospinal fluid or positron emission tomography (PET) imaging for Alzheimer's disease (AD) screening and diagnosis. This study evaluated the diagnostic performance of the fully automated HISCL plasma Aβ42/40 assay in a real-world clinical setting. Methods: We retrospectively enrolled 127 participants, stratified into cognitively normal (CN), mild cognitive impairment (MCI), AD, and Non-AD subgroups. Plasma Aβ42/40 levels were quantified using the HISCL and Simoa platforms. Additionally, plasma oligomerized Aβ (OAβ), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) were measured. Results: The HISCL plasma Aβ42/40 ratio was significantly lower in the AD continuum (MCI + AD) compared to the CN subgroup (p < 0.001). The HISCL assay demonstrated robust diagnostic performance (AUC = 0.747), yielding a comparably higher AUC value compared to the Simoa Aβ42/40 ratio (AUC = 0.687). Although method comparison showed a proportional difference between HISCL and Simoa, the HISCL assay maintained high discriminative capability. Notably, integrating plasma GFAP and NfL with the HISCL Aβ42/40 ratio significantly enhanced the diagnostic accuracy (AUC = 0.823, p = 0.046). Method comparison between heparinized and EDTA plasma in the HISCL assay confirmed assay stability, showing a significant correlation and a regression slope near unity. Conclusions: The HISCL plasma Aβ42/40 assay demonstrates reliable diagnostic performance for identifying AD pathology in clinical practice, showing stability across sample types. Furthermore, its combination with neurodegeneration markers significantly improves predictive accuracy, supporting its utility as a robust screening tool and foundational component of future multimarker diagnostic panels.