title: Synthetic Aβ peptides acquire prion-like properties in the brain.
abstract: In transmission studies with Alzheimer's disease (AD) animal models, the formation of Aβ plaques is proposed to be initiated by seeding the inoculated amyloid β (Aβ) peptides in the brain. Like the misfolded scrapie prion protein (PrPSc) in prion diseases, Aβ in AD shows a certain degree of resistance to protease digestion while the biochemical basis for protease resistance of Aβ remains poorly understood. Using in vitro assays, histoblotting, and electron microscopy, we characterize the biochemical and morphological features of synthetic Aβ peptides and Aβ isolated from AD brain tissues. Consistent with previous observations, monomeric and oligomeric Aβ species extracted from AD brains are insoluble in detergent buffers and resistant to digestions with proteinase K (PK). Histoblotting of AD brain tissue sections exhibits an increased Aβ immunoreactivity after digestion with PK. In contrast, synthetic Aβ40 and Aβ42 are soluble in detergent buffers and fully digested by PK. Electron microscopy of Aβ40 and Aβ42 synthetic peptides shows that both species of Aβ form mature fibrils. Those generated from Aβ40 are longer but less numerous than those made of Aβ42. When spiked into human brain homogenates, both Aβ40 and Aβ42 acquire insolubility in detergent and resistance to PK. Our study favors the hypothesis that the human brain may contain cofactor(s) that confers the synthetic Aβ peptides PrPSc-like physicochemical properties.
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Xiangzhu
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.|National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, Ohio, USA.|Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy.
authors.forename: Ignazio
authors.initials: I
authors.lastname: Cali
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Jue
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.|National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Cracco
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Curtiss
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.|The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, The People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Mai
authors.initials: M
authors.lastname: Abouelsaad
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Gazgalis
authors.affiliation: The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, The People's Republic of China.
authors.forename: Gong-Xian
authors.initials: GX
authors.lastname: Wang
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.|Department of Neurology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Qingzhong
authors.initials: Q
authors.lastname: Kong
authors.affiliation: Department of Pharmacology and EM Facility, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Fujioka
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.|Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Puoti
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, Ohio, USA.Department of Neurology, Case Western Reserve University, Cleveland, Ohio, USA.National Center for Regenerative Medicine, Case Western Reserve University, Cleveland, Ohio, USA.The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, The People's Republic of China.
authors.forename: Wen-Quan
authors.initials: WQ
authors.lastname: Zou
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage* / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011328:Prions / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D011328:Prions