Novel alpha-synuclein-immunoreactive proteins in brain samples from the Contursi kindred, Parkinson's, and Alzheimer's disease

A specific mutation (A53T) in the encoding region for alpha-synuclein has b een identified in a large multigenerational family with an autosomal domina nt parkinsonism known as the Contursi kindred. In this study, we used a mon oclonal antibody directed against alpha-synuclein in order to identify nove l proteins in the brain of an affected member of this kindred who had come to autopsy. Homogenates from the frontal cortex and caudate nucleus were ex amined using Western blot techniques and compared to matched autopsy specim ens from control subjects and patients with various forms of parkinsonism. Western blots, using a 15-min exposure time, revealed the expected 19-kDa b and representing alpha-synuclein in all brain samples examined. However, a novel band in the 36-kDa range was also present in the Contursi brain which was not seen in cortex or caudate from control brains or in frontal cortex hom 14 cases of typical Parkinson's disease. With a 24-h exposure time, th is band was faintly seen in the caudate nucleus of three of the Parkinson's disease cases. Surprisingly the 36-kDa band (as well as other high-molecul ar-weight bands) was also present in frontal cortex and caudate nucleus in 3 additional cases that met diagnostic criteria for both Parkinson's diseas e and Alzheimer's disease. A preliminary analysis of samples from the front al cortex of 10 Alzheimer's disease cases revealed a 36-kDa band in only on e instance. The identification of novel alpha-synuclein-immunoreactive band s in these various forms of parkinsonism may open new research avenues for exploring the relationship between abnormal protein deposition in the brain and one or more neurodegenerative disorders, including the Contursi form o f familial parkinsonism. (C) 1998 Academic Press.