Previous genetic analysis of the familial Parkinson's disease Contursi kindred led to the identification of an Ala53Thr pathogenic mutation in the α-synuclein gene. We have re-examined one of the original brains from this kindred using new immunohistochemical reagents, thioflavin S staining and immunoelectron microscopy. Surprisingly, we uncovered a dense burden of α-synuclein neuritic pathology and rare Lewy bodies. Immunoelectron microscopy demonstrated fibrillar α-synuclein-immunoreactive aggregates. Unexpected tau neuritic and less frequent perikaryal inclusions were also observed. Some inclusions were comprised of both proteins with almost complete spatial disparity. We suggest that it is important to recognize that the neurodegenerative process caused by the Ala53Thr mutation in α-synuclein is not identical to that seen in typical idiopathic Parkinson's disease brain.
All Science Journal Classification (ASJC) codes
- Clinical Neurology
- Cellular and Molecular Neuroscience
- Pathology and Forensic Medicine
- Lewy bodies
- Parkinson's disease