, Volume 99, Issue 6, pp 663-672

Distinctive neuropathology revealed by α-synuclein antibodies in hereditary parkinsonism and dementia linked to chromosome 4p

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The identification of the α-synuclein gene on chromosome 4q as a locus for familial Lewy-body parkinsonism and of α-synuclein as a component of Lewy bodies has heralded a new era in the study of Parkinson’s disease. We have identified a large family with Lewy body parkinsonism linked to a novel locus on chromosome 4p15 that does not have a mutation in the α-synuclein gene. Here we report the clinical and neuropathological findings in an individual from this family and describe unusual high molecular weight α-synuclein-immunoreactive proteins in brain homogenates from brain regions with the most marked neuropathology. Distinctive histopathology was revealed with α-synuclein immunostaining, including pleomorphic Lewy bodies, synuclein-positive glial inclusions and widespread, severe neuritic dystrophy. We also discuss the relationship of this familial disorder to a Lewy body disease clinical spectrum, ranging from Parkinson’s disease to dementia with psychosis.