alpha-synuclein expression in substantia nigra and cortex in Parkinson's disease

Mutations in the human alpha-synuclein gene have been identified in several families of European descent with early-onset Parkinson's disease (PD). We sequenced the complete alpha-synuclein cDNA from substantia nigra and cort ex from nine patients with PD and eight control subjects. No mutations were found. We then analyzed alpha-synuclein mRNA levels using a ribonuclease p rotection assay. Two major protected bands of alpha-synuclein mRNA, possibl y representing two splice variants of the gene, were observed. alpha-synucl ein mRNA was significantly diminished in the substantia nigra of patients w ith PD compared with control subjects but not in the cortex. Our findings s uggest that decreased synuclein mRNA may be an early alteration in the SN i n PD, and imply that decreased levels of the protein may play a role in the pathogenesis of sporadic cases of the disease.