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Vol. 26, No. 1, 2008
Issue release date: July 2008
Dement Geriatr Cogn Disord 2008;26:32–42

Alpha- and Gamma-Synuclein Proteins Are Present in Cerebrospinal Fluid and Are Increased in Aged Subjects with Neurodegenerative and Vascular Changes

Mukaetova-Ladinska E.B. · Milne J. · Andras A. · Abdel-All Z. · Cerejeira J. · Greally E. · Robson J. · Jaros E. · Perry R. · McKeith I.G. · Brayne C. · Xuereb J. · Cleghorn A. · Doherty J. · McIntosh G. · Milton I.
aInstitute for Ageing and Health, bDepartment of Neuropathology, Newcastle University, and cNOVOCASTRA Laboratories Ltd., Newcastle upon Tyne, and dDepartment of Public Health and Primary Care, and eDepartment of Pathology, University of Cambridge, Cambridge, UK

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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.

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