Cerebrospinal fluid α-synuclein contributes to the differential diagnosis of Alzheimer's disease

Min Shi, Lu Tang, Jon B. Toledo, Carmen Ginghina, Hua Wang, Patrick Aro, Poul H. Jensen, Daniel Weintraub, Alice S. Chen-Plotkin, David J. Irwin, Murray Grossman, Leo McCluskey, Lauren B. Elman, David A. Wolk, Edward B. Lee, Leslie M. Shaw, John Q. Trojanowski, Jing Zhang

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Introduction: The ability of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers (amyloid β peptide 1–42, total tau, and phosphorylated tau) to discriminate AD from related disorders is limited. Biomarkers for other concomitant pathologies (e.g., CSF α-synuclein [α-syn] for Lewy body pathology) may be needed to further improve the differential diagnosis. Methods: CSF total α-syn, phosphorylated α-syn at Ser129, and AD CSF biomarkers were evaluated with Luminex immunoassays in 367 participants, followed by validation in 74 different neuropathologically confirmed cases. Results: CSF total α-syn, when combined with amyloid β peptide 1–42 and either total tau or phosphorylated tau, improved the differential diagnosis of AD versus frontotemporal dementia, Lewy body disorders, or other neurological disorders. The diagnostic accuracy of the combined models attained clinical relevance (area under curve ∼0.9) and was largely validated in neuropathologically confirmed cases. Discussion: Combining CSF biomarkers representing AD and Lewy body pathologies may have clinical value in the differential diagnosis of AD.

Original languageEnglish (US)
Pages (from-to)1052-1062
Number of pages11
JournalAlzheimer's and Dementia
Issue number8
StatePublished - Aug 2018


  • Alzheimer's disease
  • Biomarkers
  • Cerebrospinal fluid
  • Differential diagnosis
  • α-synuclein

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience


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