title: Regional distribution of proteinase K-resistant alpha-synuclein correlates with Lewy body disease stage.
abstract: Lewy bodies (LBs) containing alpha-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 alphaSYN 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.
authors.affiliation: Institute of Neuropathology, Laboratory of Alzheimer's and Parkinson's Disease Research, Ludwig Maximilians University, Munich, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Neumann
authors.forename: Veronika
authors.initials: V
authors.lastname: Müller
authors.forename: Hans A
authors.initials: HA
authors.lastname: Kretzschmar
authors.forename: Christian
authors.initials: C
authors.lastname: Haass
authors.forename: Philipp J
authors.initials: PJ
authors.lastname: Kahle
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D001933:Brain Stem / Q000378:metabolism; D004351:Drug Resistance; D019286:Endopeptidase K / Q000378:metabolism*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D020961:Lewy Body Disease / Q000378:metabolism / Q000503:physiopathology*; D008032:Limbic System / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019579:Neocortex / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016612:Paraffin Embedding; D051843:Synucleins; D014018:Tissue Distribution; D051844:alpha-Synuclein
chemical_list: D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D019286:Endopeptidase K