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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 Aβ1‐40, Aβ1‐42, 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 Aβ1‐40, Aβ1‐42, p‐tau181, and tau using commercially available plasma samples on a fully automated immunoassay platform, HISCLTM 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. [ABSTRACT FROM AUTHOR]

Background: There have been a lot of studies on classification of Alzheimer's disease (AD) based on its pathological process. These pathological changes have been defined by the ATN classification system (A : amyloid β (Aβ) deposition, T : pathogenic tau, N : neurodegeneration) based on cerebrospinal fluid (CSF) biomarker levels or neuroimaging. In order to promote research and practical application, it is necessary to develop a cost effective and minimally invasive technology. Therefore, we have developed plasma Aβ1‐40, Aβ1‐42, threonine‐181 phosphorylated tau (p‐tau181) and total‐tau immunoassay systems and reported that these plasma biomarkers levels were significantly different between AD and cognitively normal (CN). In this study we have measured biomarkers in other sample sets including mild cognitive impairment (MCI), and evaluated the performance in characterizing AD pathology, in the context of the ATN classification system. Method: We measured commercially available plasma and CSF samples on the HISCLTM series, which can achieve high degrees of sensitivity and fast measurement times of 17 minutes, requiring only 10 to 30 µl of samples. The concentration of plasma and CSF biomarkers levels (Aβ1‐40, Aβ1‐42, p‐tau181, total‐tau) were measured and the significance of the difference between AD, MCI and CN groups was assessed. Result: The AD group had lower Aβ1‐42/Aβ1‐40 ratio and higher levels of p‐tau181 and t‐tau compared to MCI or CN groups. The levels of plasma biomarkers in MCI group showed wide distribution compared to AD or CN group, suggesting these plasma biomarkers reflect the various pathological states of dementia in MCI patients. This might indicate that our plasma biomarker measurement systems represent characterization of AD pathological processes. Conclusion: Our assay system revealed that the distribution of plasma biomarkers showed characteristic distribution in AD, MCI and CN groups, respectively. This result may indicate the possibility of practical diagnosis of AD pathology based on plasma biomarker ATN classification system. We aim to continue to measure other clinical sample sets for evaluation of the usefulness and universality of plasma biomarkers. [ABSTRACT FROM AUTHOR]