Assay of Plasma Phosphorylated Tau Protein (Threonine 181) and Total Tau Protein in Early-Stage Alzheimer’s Disease

Article type: Research Article

Authors: Yang, Che-Chuan^a | Chiu, Ming-Jang^{b; c; d; e} | Chen, Ta-Fu^b | Chang, Hui-Ling^a | Liu, Bing-Hsien^a | Yang, Shieh-Yueh^{a; *}

Affiliations: [a] MagQu Co., Ltd., Xindian District, New Taipei City, Taiwan | [b] Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan | [c] Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan | [d] Department of Psychology, National Taiwan University, Taipei, Taiwan | [e] Graduate Institute of Biomedical Engineering and Bioinformatics, National Taiwan University, Taipei, Taiwan

Correspondence: [*] Correspondence to: Shieh-Yueh Yang, MagQu Co., Ltd., Xindian District, New Taipei City 231, Taiwan. E-mail: [email protected].

Abstract: The feasibility of assaying plasma phosphorylated tau protein (threonine 181), denoted p-tau181, using immunomagnetic reduction (IMR) is explored. The reagent for assaying p-tau181 with IMR was synthesized, and its analytic performances were characterized. Seventy-three subjects were recruited. Each participant was examined with neuropsychological tests, magnetic resonance imaging, and IMR assay for plasma p-tau181. Using commercially available IMR kits, the plasma total tau protein (T-tau) of each subject was assayed. The dynamic range for assaying p-tau181 using IMR was 1.96×10-2 pg/ml to 104 pg/ml. There was no significant interference from total tau protein in the assay of p-tau181. The measured concentrations of plasma p-tau181 were 2.46±1.09 pg/ml for healthy controls, 4.41±1.85 pg/ml for MCI due to AD, and 6.14±1.59 pg/ml for very mild AD. Meanwhile, the measured concentrations of plasma T-tau were 18.85±10.16 pg/ml for healthy controls, 32.98±10.18 pg/ml for MCI due to AD, and 37.54±12.29 pg/ml for very mild AD. A significant difference in plasma p-tau181 was observed between healthy controls and MCI due to AD (p < 0.001) and between MCI due to AD and very mild AD (p < 0.001). However, for the plasma T-tau concentration, a significant difference existed only between healthy controls and MCI due to AD (p < 0.001). This implies that the plasma p-tau181 level is correlated more to AD severity than plasma T-tau is. Additionally, p-tau181 was observed as approximately 14% of T-tau in human plasma.

Keywords: Alzheimer’s disease, human plasma, immunomagnetic reduction, phosphorylated tau protein, total tau protein

DOI: 10.3233/JAD-170810

Journal: Journal of Alzheimer's Disease, vol. 61, no. 4, pp. 1323-1332, 2018