Measurements of auto‐antibodies to α‐synuclein in the serum and cerebral spinal fluids of patients with Parkinson's disease
Open accessAbstract
Biomarkers for α‐synuclein are needed for diagnosis and prognosis in Parkinson's disease (PD). Endogenous auto‐antibodies to α‐synuclein could serve as biomarkers for underlying synucleinopathy, but previous assessments of auto‐antibodies have shown variability and inconsistent clinical correlations. We hypothesized that auto‐antibodies to α‐synuclein could be diagnostic for PD and explain its clinical heterogeneity. To test this hypothesis, we developed an enzyme‐linked immunosorbent assay for measuring α‐synuclein auto‐antibodies in human samples. We evaluated 69 serum samples (16 healthy controls (HC) and 53 PD patients) and 145 CSF samples (52 HC and 93 PD patients) from our Institution. Both serum and CSF were available for 24 participants. Males had higher auto‐antibody levels than females in both fluids. CSF auto‐antibody levels were significantly higher in PD patients as compared with HC, whereas serum levels were not significantly different. CSF auto‐antibody levels did not associate with amyloid‐β 1–42, total tau, or phosphorylated tau. CSF auto‐antibody levels correlated with performance on the Montreal Cognitive Assessment, even when controlled for CSF amyloidβ 1–42. CSF hemoglobin levels, as a proxy for contamination of CSF by blood during lumbar puncture, did not influence these observations. Using recombinant α‐synuclein with N‐ and C‐terminal truncations, we found that CSF auto‐antibodies target amino acids 100 through 120 of α‐synuclein. We conclude that endogenous CSF auto‐antibodies are significantly higher in PD patients as compared with HC, suggesting that they could indicate the presence of underlying synucleinopathy. These auto‐antibodies associate with poor cognition, independently of CSF amyloidβ 1–42, and target a select C‐terminal region of α‐synuclein. image Read the Editorial Highlight for this article on page 433.
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Autoimmunity may play a role in the pathogenesis of Parkinson's disease, although it is unclear whether alpha-synuclein antibodies are pathogenic.
“These findings suggest that autoimmunity may play a role in the pathogenesis of Parkinson's disease, although it is unclear yet whether a-synuclein antibodies are pathogenic.”
From The role of gut dysbiosis in Parkinson’s disease: mechanistic insights and therapeutic options (2021) · cites this paper as [96]
The level of autoantibodies to alpha-synuclein has been found to be significantly increased in CSF and associated with impaired cognition in patients with Parkinson's disease.
“The level of autoantibodies to asynuclein has been found to be significantly increased in CSF and associated with impaired cognition in patients with Parkinson's disease.96”
From The role of gut dysbiosis in Parkinson’s disease: mechanistic insights and therapeutic options (2021) · cites this paper as [96]
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- Authors
- Akhtar, R. S., Licata, J. P., Luk, K. C., Shaw, L. M., Trojanowski, J. Q., & Lee, V. M. ‐.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Akhtar, Rizwan S.
- ORCID
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2018-06
- Volume
- 145
- Issue
- 6
- Pages
- 489-503
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- PMC
- PMC6030437
- OpenAlex
- W2790314308
- Cited by
- 60
- References
- 63
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 8 · 2023: 10 · 2022: 13 · 2021: 7 · 2020: 6 · 2019: 4 · 2018: 5
- FWCI
- 3.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (P50‐NS053488, P30‐AG010124, K08‐NS093127)
- American Brain Foundation
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- Parkinson's disease, cerebrospinal fluid biomarkers, serum biomarkers, synucleinopathies, cognitive impairment, amyloid-beta 42, tau protein, epitope mapping, sex differences
- MeSH terms
- Aged, Aged, 80 and over, Aging, Apolipoproteins E, Autoantibodies, Female, Genotype, Humans, Male, Middle Aged, Parkinson Disease, Peptide Fragments, Psychomotor Performance, Sex Characteristics, Amyloid beta-Peptides, tau Proteins, alpha-Synuclein
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