title: Morphological and biochemical analyses of amyloid plaque core proteins purified from Alzheimer disease brain tissue.
abstract: Amyloid plaque cores were purified from Alzheimer disease brain tissue. Plaque core proteins were solubilized in formic acid which upon dialysis against guanidinium hydrochloride (GuHCl) partitioned into soluble (approximately 15%) and insoluble (approximately 85%) components. The GuHCl-soluble fraction contained beta-amyloid1-40, whereas the GuHCl-insoluble fraction was fractionated into six components by size exclusion HPLC: S1 (> 200 kDa), S2 (200 kDa), S3 (45 kDa), S4 (15 kDa), S5 (10 kDa), and S6 (5 kDa). Removal of the GuHCl reconstituted 10-nm filaments composed of two intertwined 5-nm strands. Fractions S5 and S6 also yielded filamentous structures when treated similarly, whereas fractions S1-S4 yielded amorphous aggregates. Chemical analysis identified S4-S6 as multimeric and monomeric beta-amyloid. Immunochemical analyses revealed alpha 1-antichymotrypsin and non-beta-amyloid segments of the beta-amyloid precursor protein within fractions S1 and S2. Several saccharide components were identified within plaque core protein preparations by fluorescence and electron microscopy, as seen with fluorescein isothiocyanate- and colloidal gold-conjugated lectins. We have shown previously that this plaque core protein complex is more toxic to neuronal cultures than beta-amyloid. The non-beta-amyloid components likely mediate this additional toxicity, imposing a significant influence on the pathophysiology of Alzheimer disease.
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201.
authors.forename: A E
authors.initials: AE
authors.lastname: Roher
authors.forename: K C
authors.initials: KC
authors.lastname: Palmer
authors.forename: E C
authors.initials: EC
authors.lastname: Yurewicz
authors.forename: M J
authors.initials: MJ
authors.lastname: Ball
authors.forename: B D
authors.initials: BD
authors.lastname: Greenberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D000596:Amino Acids / Q000032:analysis; D000682:Amyloid / Q000032:analysis* / Q000737:chemistry* / Q000648:ultrastructure; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000737:chemistry* / Q000648:ultrastructure; D016564:Amyloid beta-Protein Precursor / Q000032:analysis / Q000737:chemistry; D001921:Brain / Q000473:pathology* / Q000648:ultrastructure; D002241:Carbohydrates / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D037102:Lectins; D046911:Macromolecular Substances; D008297:Male; D008854:Microscopy, Electron; D016253:Microscopy, Immunoelectron
chemical_list: D000596:Amino Acids; D000682:Amyloid; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D002241:Carbohydrates; D037102:Lectins; D046911:Macromolecular Substances