Investigation of tau post-translationanl modification based on T217 and T231 in human plasma as new biomarkers

Abstract

Background: Post-translational modification (PTM) of human tau protein is of high importance as an indicator for predicting the progress of Alzheimer’s disease (AD). Particularly, phosphorylation and O-glycosylation on tau have been observed at relatively high levels in Alzheimer’s disease (AD) patients and healthy controls, respectively [1]. Recently, a study reported that an increase in the level of phosphorylation at T217 and T231 was observed in the initial stages of the preclinical Alzheimer’s continuum [2]. Reference: [1] C. Alquezar et al. Frontiers in Neurology, 11 (2021) 595532. [2] Marc Su？rez-Calvet et al. EMBO Molecular Medicine, 12 (2020) e12921. Method: To investigate the PTM of tau protein in human blood plasma, an electrochemical sensor with 1 μm gap between working and counter electrodes was performed and obtained Taumeter indicating the ratio of phosphorylation and O-glycosylation on the surface of tau protein, where antibodies for phosphorylated T217 and T231 were used [3]. To explore the clinical association, standardized uptake value ratio (SUVR) of amyloid-positron emission tomography (PET), mini-mental state examination (MMSE), and clinical dementia rating scale sum of boxes (CDR-SB) were also investigated and compared to Taumeters. Reference: [3] Yoon et al. Alzheimer&apos;s & Dementia, 18 (2022) e061465. Result: A total of 43 participants (normal control (NC, n=15), mild cognitive impairment (MCI, n=14), and AD (n=14) were investigated. Taumeters for T217 (p=0.00423, AUC=0.82667) and T231 (p=0.00034, AUC=0.86222) were obtained and analyzed through one-way analysis of variance (ANOVA) between NC and AD groups (Figure 2). In regression analysis, Taumeter for T217 (r=0.23824, p=0.12394) was more correlated with amyloid-PET SUVR than Taumeter for T231 (r=0.28072, p=0.06824) (Figures 3a-b). Taumeter for T217 (r =-0.51246, p=0.00044) was also more correlated with MMSE score than Taumeter for T231 (r=-0.07186, p=0.64701) (Figures 3c-d). Taumeter for T217 (r=0.57937, p<0.0001) was more correlated with the CDR-SB score than Taumeter for T231 (r=0.16254, p=0.29768) (Figures 3e-f). Conclusion: In this study, we investigated the correlation between Taumeters for T217 and T231, amyloid-PET SUVR, MMSE score, and CDR-SB score. As a result, Taumeter for T217 indicates more strong correlation with analytical results of amyloid-PET SUVR, MMSE score, and CDR-SB score than Taumter for T231.