Development of fully automated plasma immunoassay using by HISCL ^TM series for classification of neurological disorders

Background ATN classification system (A: β‐amyloid (Aβ) deposition, T: pathogenic tau accumulation, N: neurodegeneration) has been widely accepted as a research framework for not only characterization of Alzheimer's disease (AD), but also for discrimination of AD from other neurological disorders (OND) such as Parkinson disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Currently, the different pathological processes are represented by the biomarker normality/abnormality which is diagnosed by neuroimaging and/or measuring the biomarker levels in cerebrospinal fluid. A simple diagnostic method needs to be established to evaluate pathological processes in routine clinical practice. Blood‐based biomarkers would be appropriate for clinical applications because of their simplicity and accessibility. We have developed plasma Aβ 1‐40 , Aβ 1‐42 , threonine‐181 phosphorylated tau (p‐tau181), and tau immunoassays and reported that the plasma biomarker levels were significantly different between AD, mild cognitive impairment (MCI), and cognitively normal (CN) groups, suggesting the possibility of characterizing AD. Here, we present the results of the ATN biomarker profile of OND samples using our fully automated assay. Method We measured Aβ 1‐40 , Aβ 1‐42 , p‐tau181, and tau using commercially available plasma samples on a fully automated immunoassay platform, HISCL TM series. The platform can achieve high degrees of sensitivity and requires only 30 µl of sample and 17 minutes to complete the measurement per assay. The plasma ATN biomarker profiles were evaluated in AD, MCI, CN, and OND groups. Result All plasma biomarker levels were significantly different between the AD and CN groups. Plasma p‐tau181 showed the most significant difference between the AD group and OND group. The median plasma p‐tau181 concentration in AD groups was more than twice higher compared to OND groups. Conclusion Our results indicated the possibility of discriminating AD from OND by plasma p‐tau181 and tau levels. Our fully automated plasma assay system may have a potential to be a simple diagnostic method to evaluate the pathological process in routine clinical practice for discriminating AD from OND based on ATN classification system.