Expression of alpha-synuclein in the human brain: relation to Lewy body disease

alpha -Synuclein is mutated in some hereditary cases of Parkinson's disease and the protein precipitates in Lewy bodies, the pathological hallmark of both Parkinson's disease and Lewy body disease. Transgenic mice overexpress ing human wild-type alpha -synuclein develop alpha -synuclein-immunoreactiv e inclusions in brain regions typically affected with Lewy body disease. We used in situ hybridization to characterize alpha -synuclein expression and examine mRNA levels in patients affected with Lewy body disease and contro ls. Substantia nigra was avoided because of the extensive neuronal loss and cingulate gyrus was chosen as it is one of the diagnostic regions in Lewy body disease where Lewy bodies most frequently are demonstrated. beta -tubu lin was used to control for neuronal degeneration. The a-synuclein probe sh owed intense labeling of pyramidal cells in lamina III and V in both patien ts and controls. We found no difference in alpha -synuclein mRNA levels and beta -tubulin mRNA was not significantly altered (P=0.06) in patient brain s. There was no difference in the ratio of alpha -Synuclein and beta -tubul in mRNA levels between patients and controls. Further, we found no relation ship between alpha -synuclein mRNA levels and Lewy bodies. Great variabilit y in alpha -synuclein mRNA levels among patients indicates that Lewy body d isease may be a heterogeneous disorder with regard to alpha -synuclein invo lvement. (C) 2001 Elsevier Science BY. All rights reserved.