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Alpha- and gamma-synuclein proteins are present in cerebrospinal fluid and are increased in aged subjects with neurodegenerative and vascular changes

Lookup NU author(s): Dr Elizabeta Mukaetova-Ladinska, Joan Milne, Dr Alina Andras, Zeinab Abdel-All, Liz Greally, Dr Evelyn Jaros, Emeritus Professor Robert Perry, Professor Ian McKeith, Professor Carol Brayne


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Background: Disease-specific biomarkers should reflect a fundamental feature of neuropathology and be validated in neuropathologically confirmed cases. Several synaptic proteins have been described in cerebrospinal fluid (CSF) of patients with dementia. In Lewy body disease α-synuclein is incorporated within Lewy bodies and α-, β- and γ-synucleins in dystrophic neuritis. These pathological changes are expected to be seen in CSF. Methods: A total of 25 CSF post-mortem samples (8 control and 17 subjects with dementia) were used to quantify α- and γ-synucleins and IgG. Results: We describe for the first time the presence of γ-synuclein in CSF. There is an elevation of both α- and γ-synucleins in CSF from elderly individuals with Alzheimer's disease, Lewy body disease (LBD) and vascular dementia (CVD), compared to normal controls. γ-Synuclein showed a greater elevation in LBD, IgG in CVD. The elevation of α- and γ-synucleins was seen from Braak stage III onwards and remained stable until Braak stage VI. These results were not influenced by age at death or post-mortem delay. Conclusions: The reported increases in α- and γ-synucleins and IgG in the ventricular CSF of individuals with dementia are novel findings. They now need to be explored further using a greater number of cases in each subgroup, using lumbar CSF samples to determine their applicability and relevance to a clinical diagnostic setting. It needs to be established whether using these markers may help to discriminate LBD from other types of neurodegenerative and vascular dementias. Copyright © 2008 S. Karger AG.

Publication metadata

Author(s): Mukaetova-Ladinska EB, Milne J, Andras A, Abdel-All Z, Cerejeira J, Greally E, Robson J, Jaros E, Perry R, McKeith IG, Brayne C, Xuereb J, Cleghorn A, Doherty J, McIntosh G, Milton I

Publication type: Article

Publication status: Published

Journal: Dementia and Geriatric Cognitive Disorders

Year: 2008

Volume: 26

Issue: 1

Pages: 32-42

ISSN (print): 1420-8008

ISSN (electronic): 1421-9824

Publisher: S. Karger AG


DOI: 10.1159/000141039


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Funder referenceFunder name
G0400074Medical Research Council
G0502157Medical Research Council
G9901400Medical Research Council