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