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

Abstract

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.

Variant in the 3′ region of SNCA associated with Parkinson’s disease and serum α-synuclein levels

“…Several studies have reported decreased a-synuclein levels in extracellular fluids in PD patients and patients with other synucleinopathies [16,19,22,26,27,37], while other studies have reported increased a-synuclein levels in PD patients [21,29]. Although neither change was replicated in our study, the association between the risk-associated allele T and decreased serum a-synuclein levels partly supports the former group of studies.…”

The role of α-synuclein in neurodegeneration — An update

“…Similar to divergent results on the plasma levels of AS in PD [765][766][767], retrospective studies of CSF provided inconclusive and contradictory results [731,760,[768][769][770][771]. pAS was detected in PD samples, which was not the case for oligoAS or oligo-pAS [772].…”

Alzheimer’s Diseases: Towards Biomarkers for an Early Diagnosis

“…Moreover, oligomeric forms of -Syn were detected in CSF and blood of patients with Parkinson disease (El-Agnaf, . Nevertheless, several studies are conflicting since elevated or normal CSF levels were also observed in DLB patients (Mukaetova-Ladinska, Milne et al 2008;Spies, Melis et al 2009;Ballard, Jones et al 2010). In the same way, we can postulate an association of typical CSF biomarkers of AD with prion CSF measurement since neuropathology of CJD is more intricate than we though it several years ago (Kovacs, Seguin et al 2011). …”