Alzheimer’s Research & Therapy (Jul 2020)

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,
  • for the Alzheimer’s Disease All Markers (ADAM) Research group

DOI
https://doi.org/10.1186/s13195-020-00648-9
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 12

Abstract

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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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