title: The solubility of alpha-synuclein in multiple system atrophy differs from that of dementia with Lewy bodies and Parkinson's disease.
abstract: Intracellular inclusions containing alpha-synuclein (alpha SN) are pathognomonic features of several neurodegenerative disorders. Inclusions occur in oligodendrocytes in multiple system atrophy (MSA) and in neurons in dementia with Lewy bodies (DLB) and Parkinson's disease (PD). In order to identify disease-associated changes of alpha SN, this study compared the levels, solubility and molecular weight species of alpha SN in brain homogenates from MSA, DLB, PD and normal aged controls. In DLB and PD, substantial amounts of detergent-soluble and detergent-insoluble alpha SN were detected compared with controls in grey matter homogenate. Compared with controls, MSA cases had significantly higher levels of alpha SN in the detergent-soluble fraction of brain samples from pons and white matter but detergent-insoluble alpha SN was not detected. There was an inverse correlation between buffered saline-soluble and detergent-soluble levels of alpha SN in individual MSA cases suggesting a transition towards insolubility in disease. The differences in solubility of alpha SN between grey and white matter in disease may result from different processing of alpha SN in neurons compared with oligodendrocytes. Highly insoluble alpha SN is not involved in the pathogenesis of MSA. It is therefore possible that buffered saline-soluble or detergent-soluble forms of alpha SN are involved in the pathogenesis of other alpha SN-related diseases.
authors.affiliation: Department of Pathology, The University of Melbourne, Victoria, Australia.
authors.forename: B C
authors.initials: BC
authors.lastname: Campbell
authors.forename: C A
authors.initials: CA
authors.lastname: McLean
authors.forename: J G
authors.initials: JG
authors.lastname: Culvenor
authors.forename: W P
authors.initials: WP
authors.lastname: Gai
authors.forename: P C
authors.initials: PC
authors.lastname: Blumbergs
authors.forename: P
authors.initials: P
authors.lastname: Jäkälä
authors.forename: K
authors.initials: K
authors.lastname: Beyreuther
authors.forename: C L
authors.initials: CL
authors.lastname: Masters
authors.forename: Q X
authors.initials: QX
authors.lastname: Li
mesh_terms: D000368:Aged; D015153:Blotting, Western; D001923:Brain Chemistry; D002531:Cerebellum / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D005625:Frontal Lobe / Q000737:chemistry; D006801:Humans; D020961:Lewy Body Disease / Q000378:metabolism*; D008875:Middle Aged; D008970:Molecular Weight; D019578:Multiple System Atrophy / Q000209:etiology / Q000378:metabolism*; D009186:Myelin Sheath / Q000737:chemistry / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry; D009836:Oligodendroglia / Q000737:chemistry; D010300:Parkinson Disease / Q000378:metabolism*; D011149:Pons / Q000737:chemistry; D012016:Reference Values; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D012995:Solubility; D051843:Synucleins; D051844:alpha-Synuclein
chemical_list: D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D012967:Sodium Dodecyl Sulfate