CSF total tau/α-synuclein ratio improved the diagnostic performance for Alzheimer's disease as an indicator of tau phosphorylation
- Authors
- Shim, Kyu Hwan; Kang, Min Ju; Suh, Jee Won; Pyun, Jung-Min; Ryoo, Nayoung; Park, Young Ho; Youn, Young Chul; Jang, Jae-Won; Jeong, Jee Hyang; Park, Kyung Won; Choi, Seong Hye; Suk, Kyoungho; Lee, Ho-Won; Ko, Pan-Woo; Lee, Chan-Nyoung; Lim, Tae-Sung; An, Seong Soo A.; Kim, SangYun
- Issue Date
- Jul-2020
- Publisher
- BMC
- Keywords
- Alzheimer’s disease; Biomarker; Cerebrospinal fluid; Tau; α-Synuclein
- Citation
- Alzheimer's research & therapy, v.12, no.1, pp.83 - 95
- Journal Title
- Alzheimer's research & therapy
- Volume
- 12
- Number
- 1
- Start Page
- 83
- End Page
- 95
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/76177
- DOI
- 10.1186/s13195-020-00648-9
- ISSN
- 1758-9193
- 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.
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