α-Synuclein mRNA and soluble α-synuclein protein levels in post-mortem brain from patients with Parkinson's disease, dementia with Lewy bodies, and Alzheimer's disease

alpha-Synuclein is a neuronal protein implicated in the etiology of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Whilst increased alpha-synuclein expression due to gene duplication or triplication can cause familial PD, previous studies of alpha-synuclein levels in idiopathic disease have produced conflicting data. We quantified alpha-synuclein mRNA and soluble protein in five human post-mortem brain regions from four groups of individuals with PD, DLB, Alzheimer's disease (AD) and matched controls. alpha-Synuclein mRNA levels, measured using quantitative real-time PCR, did not differ significantly between groups in any brain regions examined. In contrast, levels of soluble alpha-synuclein protein, measured by ELISA, were significantly lower in 4 of the 5 regions for patients with DLB, and in 2 of the 5 regions for patients with PD, compared to controls. Soluble alpha-synuclein protein levels were not significantly different in the AD patients, compared to controls, in 4 of the 5 regions. This study indicates that although levels of soluble alpha-synuclein protein are lower in DLB and PD, there is no evidence for a corresponding decrease in alpha-synuclein mRNA levels. This might result from altered translation, or removal of alpha-synuclein protein from a soluble detectable state, either by turnover or conversion to an insoluble form. (C) 2012 Elsevier B.V. All rights reserved.