Cerebrospinal fluid α‐synuclein contributes to the differential diagnosis of Alzheimer's disease
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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.
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Numerous studies have documented unaltered or slightly increased cerebrospinal fluid αSyn levels in patients with mild cognitive impairment and Alzheimer's disease.
“numerous studies have documented unaltered or slightly increased CSF αSyn levels in patients with MCI and AD [27, 80–82, 86, 90, 91, 93, 94].”
From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [94]
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Cerebrospinal Fluid, Imaging, and Physiological Biomarkers in Dementia With Lewy Bodies
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α-synuclein as an emerging pathophysiological biomarker of Alzheimer’s disease
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- Authors
- Shi, M., Tang, L., Toledo, J. B., Ginghina, C., Wang, H., Aro, P., Jensen, P. H., Weintraub, D., Chen‐Plotkin, A. S., Irwin, D. J., Grossman, M., McCluskey, L., Elman, L. B., Wolk, D. A., Lee, E. B., Shaw, L. M., Trojanowski, J. Q., & Zhang, J.
- Affiliations
- University of Washington (US)
- University of Pennsylvania (US)
- Department of Pathology University of Washington School of Medicine Seattle WA USA
- Aarhus University (DK)
- Corresponding author
- Zhang, Jing
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2018-03-28
- Volume
- 14
- Issue
- 8
- Pages
- 1052-1062
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC6097943
- OpenAlex
- W2795342522
- Cited by
- 42
- References
- 58
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 7 · 2019: 9 · 2018: 5
- FWCI
- 5.08
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (U01 NS082137, U01 NS091272, R56 AG057417, P30 AG010124, P50 NS053488, P01 AG017586-8499)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- Alzheimer's disease, cerebrospinal fluid biomarkers
- MeSH terms
- Aged, Alzheimer Disease, Amyloid, Diagnosis, Differential, Female, Humans, Male, Phosphorylation, Biomarkers, tau Proteins, Lewy Body Disease, alpha-Synuclein
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