title: Accumulation of insoluble alpha-synuclein in dementia with Lewy bodies.
abstract: The alpha-synuclein (alpha SN) protein is thought to play a central role in the pathogenesis of neurodegenerative diseases where it aggregates to form intracellular inclusions. We have used Western blotting to examine the expression levels and solubility of alpha SN in brain homogenates from dementia with Lewy bodies (DLB), Parkinson's disease (PD), Alzheimer's disease (AD), and normal controls using samples from the parahippocampus/transentorhinal cortex. Compared to controls, DLB brains accumulate significantly greater amounts of sodium dodecyl sulfate (SDS)-soluble and SDS-insoluble alpha SN but levels of TBS-soluble alpha SN did not change. Levels of synaptophysin, a marker of synaptic integrity, were significantly lower in DLB cases than in normal aged controls regardless of whether concurrent changes of AD were present. This limbic synaptic dysfunction may contribute to cognitive impairment in DLB. Whether aggregated alpha SN is a cause or effect of the disease process in DLB and PD remains to be determined, but the presence of aggregated alpha SN is consistent with a pathogenesis similar to that associated with aggregates of Abeta amyloid in AD.
authors.affiliation: Department of Pathology, The University of Melbourne, 3010, Australia.
authors.forename: B C
authors.initials: BC
authors.lastname: Campbell
authors.forename: Q X
authors.initials: QX
authors.lastname: Li
authors.forename: J G
authors.initials: JG
authors.lastname: Culvenor
authors.forename: P
authors.initials: P
authors.lastname: Jäkälä
authors.forename: R
authors.initials: R
authors.lastname: Cappai
authors.forename: K
authors.initials: K
authors.lastname: Beyreuther
authors.forename: C L
authors.initials: CL
authors.lastname: Masters
authors.forename: C A
authors.initials: CA
authors.lastname: McLean
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000150:complications / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D018728:Entorhinal Cortex / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020961:Lewy Body Disease / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D020534:Parahippocampal Gyrus / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D012016:Reference Values; D012995:Solubility; D016708:Synaptophysin / Q000378:metabolism; D051843:Synucleins; D051844:alpha-Synuclein
chemical_list: D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D016708:Synaptophysin; D051843:Synucleins; D051844:alpha-Synuclein