title: Insoluble alpha-synuclein in Alzheimer's disease without Lewy body formation.
abstract: Insoluble alpha-synuclein plays a central role in Lewy body diseases, with considerable controversy as to whether it plays a similar role in Alzheimer's disease (AD). We assessed the tissue location and solubility of cortical alpha-synuclein in AD (without Lewy body formation) compared with controls, using sequential extraction procedures and Western immunoblotting to quantify different alpha-synuclein species in their different solubility states. Controls had no insoluble cortical alpha-synuclein and a ratio of soluble:lipid-associated alpha-synuclein of 1.2-/+0.1. Total alpha-synuclein protein was significantly increased in AD and concentrated within the lipid-associated fraction (soluble:lipid ratio 0.9-/+0.05, soluble:insoluble 1.5-/+0.1, lipid:insoluble 1.7-/+0.1) which proved difficult to localize in paraffin-embedded tissue. Tissues prepared without lipid extraction revealed alpha-synuclein-immunoreactivity in the amorphous components of mature cored AD plaques. This lipid-association of alpha-synuclein in mature AD plaques links this protein with other lipid changes thought to be important in disease pathogenesis.
authors.affiliation: Prince of Wales Medical Research Institute, Sydney, 2031 Australia.
authors.forename: Melissa
authors.initials: M
authors.lastname: Broe
authors.forename: Claire E
authors.initials: CE
authors.lastname: Shepherd
authors.forename: David M A
authors.initials: DM
authors.lastname: Mann
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Milward
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Gai
authors.forename: Emma
authors.initials: E
authors.lastname: Thiel
authors.forename: Glenda M
authors.initials: GM
authors.lastname: Halliday
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D016631:Lewy Bodies / Q000378:metabolism / Q000473:pathology; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000096:biosynthesis*; D012995:Solubility; D051843:Synucleins; D051844:alpha-Synuclein
chemical_list: D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein