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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Occurrence of alpha-synuclein pathology in the cerebellum of Guamanian patients with parkinsonism-dementia complex.

Amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/ PDC) is a progressive neurodegenerative disease affecting the indigenous Chamorro population of Guam. Neuropathologically, PDC is characterized by neuronal loss in the substantia nigra pars compacta with severe widespread neurofibrillary tangles (NFTs) similar to those observed in Alzheimer's disease (AD), and is thus considered a tauopathy. Following reports of alpha-synuclein pathology in PDC patients of Guam, PDC has also been neuropathologically classified as a synucleinopathy. Recently, the presence of alpha-synuclein-positive bodies has been reported in the cerebellum of some patients with Parkinson's disease (PD), diffuse Lewy body disease (DLBD), or multiple system atrophy (MSA). Using immunohistochemical techniques, we investigated the deposition of alpha-synuclein in the cerebellum of Guamanian PDC patients. Numerous alpha-synuclein-immunoreactive spherical structures were found in the molecular layer of the cerebellum of 63.6% of PDC patients. These structures were only seen in patients showing alpha-synuclein pathology in the amygdala. The average density of alpha-synuclein-immunoreactive structures in the cerebellum of Guamanian PDC patients was almost an order of magnitude higher than in non-Guamanian PD patients, and this alpha-synuclein pathology was much more pronounced in the hemisphere than in the vermis. In addition, double immunohistochemistry revealed that cerebellar alpha-synuclein is co-localized with the neuronal marker calbindin and with glial-fibrillary acidic protein, suggesting the involvement of Purkinje cells and Bergmann glia. These findings demonstrate that the alpha-synuclein pathology in PDC of Guam affects not only the amygdala, but also the cerebellum, where it appears to involve both Purkinje cells and specialized astrocytes.[1]


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