Journal
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
Volume 63, Issue 12, Pages 1225-1235Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/jnen/63.12.1225
Keywords
dementia; Lewy body; Parkinson disease; proteinase; synuclein
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Lewy bodies (LBs) containing a-synuclein (alphaSYN) fibrils are the hallmark lesions of Parkinson disease, dementia with LBs. and related neurodegenerative diseases. Here we have investigated the susceptibility to proteolysis of alphaSYN from brain samples of patients with different subtypes of LB diseases. While Soluble aSYN was completely degradable in all samples. the affected brain regions additionally contained insoluble, proteinase K (PK)-resistant alphaSYN. In brainstem-predominant subtype LB disease cases, PK-resistant alphaSYN was found in the medulla and substantia nigra, but not in cerebral cortex. In limbic subtype LB disease cases, PK resistance of alphaSYN spread to the cingulate and parahippocampal cortex, and further to the frontal cortex in neocortical subtype LB disease cases. Variable amounts of neuritic PK-resistant alphaSYN were found in the striatum of all cases. Thus, PK resistance of alphaSYN may be useful for the development of biomarkers of LB diseases.
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