title: Distinct synthetic Aβ prion strains producing different amyloid deposits in bigenic mice.
abstract: An increasing number of studies continue to show that the amyloid β (Aβ) peptide adopts an alternative conformation and acquires transmissibility; hence, it becomes a prion. Here, we report on the attributes of two strains of Aβ prions formed from synthetic Aβ peptides composed of either 40 or 42 residues. Modifying the conditions for Aβ polymerization increased both the protease resistance and prion infectivity compared with an earlier study. Approximately 150 d after intracerebral inoculation, both synthetic Aβ40 and Aβ42 prions produced a sustained rise in the bioluminescence imaging signal in the brains of bigenic Tg(APP23:Gfap-luc) mice, indicative of astrocytic gliosis. Pathological investigations showed that synthetic Aβ40 prions produced amyloid plaques containing both Aβ40 and Aβ42 in the brains of inoculated bigenic mice, whereas synthetic Aβ42 prions stimulated the formation of smaller, more numerous plaques composed predominantly of Aβ42. Synthetic Aβ40 preparations consisted of long straight fibrils; in contrast, the Aβ42 fibrils were much shorter. Addition of 3.47 mM (0.1%) SDS to the polymerization reaction produced Aβ42 fibrils that were indistinguishable from Aβ40 fibrils produced in the absence or presence of SDS. Moreover, the Aβ amyloid plaques in the brains of bigenic mice inoculated with Aβ42 prions prepared in the presence of SDS were similar to those found in mice that received Aβ40 prions. From these results, we conclude that the composition of Aβ plaques depends on the conformation of the inoculated Aβ polymers, and thus, these inocula represent distinct synthetic Aβ prion strains.
authors: Institute for Neurodegenerative Diseases,Departments of Neurology and.
authors: Jan
authors: J
authors: Stöhr
authors: Institute for Neurodegenerative Diseases.
authors: Carlo
authors: C
authors: Condello
authors: Institute for Neurodegenerative Diseases,Departments of Neurology and.
authors: Joel C
authors: JC
authors: Watts
authors: Institute for Neurodegenerative Diseases.
authors: Lillian
authors: L
authors: Bloch
authors: Pathology, and.
authors: Abby
authors: A
authors: Oehler
authors: Pharmaceutical Chemistry, University of California, San Francisco, CA 94143.
authors: Mimi
authors: M
authors: Nick
authors: Institute for Neurodegenerative Diseases,Pathology, and.
authors: Stephen J
authors: SJ
authors: DeArmond
authors: Institute for Neurodegenerative Diseases,Departments of Neurology and.
authors: Kurt
authors: K
authors: Giles
authors: Pharmaceutical Chemistry, University of California, San Francisco, CA 94143.
authors: William F
authors: WF
authors: DeGrado
authors: Institute for Neurodegenerative Diseases,Departments of Neurology and stanley@ind.ucsf.edu.
authors: Stanley B
authors: SB
authors: Prusiner
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D006801:Humans; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology*; D011328:Prions; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011328:Prions; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)
keywords: Alzheimer's disease; in vitro; neurodegenerative diseases