α-Synuclein in Cerebrospinal Fluid of Alzheimer's Disease and Mild Cognitive Impairment
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In addition to amyloid-β (Aβ) and tau, α-synuclein, best known for its role in Parkinson's disease (PD), has been suggested to be involved in cognition and pathogenesis of Alzheimer's disease (AD). We investigate the potential of α-synuclein in cerebrospinal fluid (CSF) as a biomarker of cognitive decline in AD, and its prodromal phase, mild cognitive impairment (MCI). Using an established, sensitive Luminex assay, we measured α-synuclein levels in the CSF of a cohort of close to 400 healthy control, MCI, and AD subjects obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and factored in APOE genotype in data analysis. CSF α-synuclein levels were significantly higher in the MCI (p = 0.005) and AD (p < 0.001) groups, compared to controls. However, receiver operating characteristic (ROC) curve analysis suggests that CSF α-synuclein level on its own only offered modest sensitivity (65%) and specificity (74%) as a diagnostic marker of AD, with an area under the curve (AUC) value of 0.719 for AD versus controls. The effect of APOE genotype, if any, was quite subtle. However, there was a significant correlation between α-synuclein and cognition (p = 0.001), with increased α-synuclein levels associated with decreased Mini-Mental State Exam scores. Our results support a role for α-synuclein even in MCI, the early phase of AD, in addition to being a potential contributor in MCI and AD diagnosis or monitoring of disease progression.
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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 [86]
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- Authors
- Korff, A., Liu, C., Ginghina, C., Shi, M., Zhang, J., & Initiative, F. T. A. D. N.
- Affiliations
- Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA
- Xiamen University (CN)
- University of Washington (US)
- Corresponding author
- Zhang, Jing
- Venue
- Journal of Alzheimer’s Disease
- Publisher
- SAGE Publications
- Published
- 2013-08-05
- Volume
- 36
- Issue
- 4
- Pages
- 679-688
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- PMC
- PMC3740054
- OpenAlex
- W1573440420
- Cited by
- 95
- References
- 41
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 10 · 2023: 5 · 2022: 8 · 2021: 7 · 2020: 7 · 2019: 11 · 2018: 11 · 2017: 3 · 2016: 7 · 2015: 7 · 2014: 9 · 2013: 3
- FWCI
- 6.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5u01ag024904-10)
- Canadian Institutes of Health Research
- National Institute on Aging (U01-AG-024904, P30AG010129, R01AG033398, K01AG030514)
- National Institute of Neurological Disorders and Stroke (U01NS082137, P50NS062684, R01NS057567)
- National Institute of Environmental Health Sciences (P30ES007033-6364, R01ES019277, P42ES004696, R01ES016873, P42 ES004696-5897, P30ES007033)
- National Institute of Biomedical Imaging and Bioengineering
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- alpha-synuclein, cerebrospinal fluid biomarkers
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Female, Humans, Male, Middle Aged, Cohort Studies, Biomarkers, alpha-Synuclein, Cognitive Dysfunction
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