CSF total tau/α-synuclein ratio improved the diagnostic performance for Alzheimer's disease as an indicator of tau phosphorylation

Kyu Hwan Shim, Min Ju Kang, Jee Won Suh, Jung-Min Pyun, Nayoung Ryoo, Young Ho Park, Young Chul Youn, Jae-Won Jang, Jee Hyang Jeong, Kyung Won Park, Seong Hye Choi, Kyoungho Suk, Ho-Won Lee, Pan-Woo Ko, Chan-Nyoung Lee, Tae-Sung Lim, Seong Soo A An, SangYun Kim

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Recently, several studies suggested potential involvements of α-synuclein in Alzheimer's disease (AD) pathophysiology. Higher concentrations of α-synuclein were reported in cerebrospinal fluid (CSF) of AD patients with a positive correlation towards CSF tau, indicating its possible role in AD. We analyzed the CSF biomarkers to verify whether α-synuclein could be an additional supported biomarker in AD diagnosis.

METHODS: In this cross-sectional study, CSF samples of 71 early-onset AD, 34 late-onset AD, 11 mild cognitive impairment, 17 subjective cognitive decline, 45 Parkinson's disease, and 32 healthy control (HC) were collected. CSF amyloid-β1-42 (A), total tau (N), and phosphorylated tau181 (T) were measured by commercial ELISA kits, and in-house ELISA kit was developed to quantify α-synuclein. The cognitive assessments and amyloid-PET imaging were also performed.

RESULTS: CSF α-synuclein manifested a tendency to increase in AD and to decreased in Parkinson's disease compared to HC. The equilibrium states of total tau and α-synuclein concentrations were changed significantly in AD, and the ratio of total tau/α-synuclein (N/αS) was dramatically increased in AD than HC. Remarkably, N/αS revealed a strong positive correlation with tau phosphorylation rate. Also, the combination of N/αS with amyloid-β1-42/phosphorylated tau181 ratio had the best diagnosis performance (AUC = 0.956, sensitivity = 96%, specificity = 87%). In concordance analysis, N/αS showed the higher diagnostic agreement with amyloid-β1-42 and amyloid-PET. Analysis of biomarker profiling with N/αS had distinctive characteristics and clustering of each group. Especially, among the group of suspected non-Alzheimer's disease pathophysiology, all A-T+N+ patients with N/αS+ were reintegrated into AD.

CONCLUSIONS: The high correlation of α-synuclein with tau and the elevated N/αS in AD supported the involvement of α-synuclein in AD pathophysiology. Importantly, N/αS improved the diagnostic performance, confirming the needs of incorporating α-synuclein as a biomarker for neurodegenerative disorders. The incorporation of a biomarker group [N/αS] could contribute to provide better understanding and diagnosis of neurodegenerative disorders.

Original languageEnglish
Pages (from-to)83
JournalAlzheimer's research & therapy
Volume12
Issue number1
DOIs
StatePublished - 13 Jul 2020

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    Shim, K. H., Kang, M. J., Suh, J. W., Pyun, J-M., Ryoo, N., Park, Y. H., Youn, Y. C., Jang, J-W., Jeong, J. H., Park, K. W., Choi, S. H., Suk, K., Lee, H-W., Ko, P-W., Lee, C-N., Lim, T-S., An, S. S. A., & Kim, S. (2020). CSF total tau/α-synuclein ratio improved the diagnostic performance for Alzheimer's disease as an indicator of tau phosphorylation. Alzheimer's research & therapy, 12(1), 83. https://doi.org/10.1186/s13195-020-00648-9