title: Strain-specific Fibril Propagation by an Aβ Dodecamer.
abstract: Low molecular weight oligomers of amyloid-β (Aβ) have emerged as the primary toxic agents in the etiology of Alzheimer disease (AD). Polymorphism observed within the aggregation end products of fibrils are known to arise due to microstructural differences among the oligomers. Diversity in aggregate morphology correlates with the differences in AD, cementing the idea that conformational strains of oligomers could be significant in phenotypic outcomes. Therefore, it is imperative to determine the ability of strains to faithfully propagate their structure. Here we report fibril propagation of an Aβ42 dodecamer called large fatty acid-derived oligomers (LFAOs). The LFAO oligomeric strain selectively induces acute cerebral amyloid angiopathy (CAA) in neonatally-injected transgenic CRND8 mice. Propagation in-vitro occurs as a three-step process involving the association of LFAO units. LFAO-seeded fibrils possess distinct morphology made of repeating LFAO units that could be regenerated upon sonication. Overall, these data bring forth an important mechanistic perspective into strain-specific propagation of oligomers that has remained elusive thus far.
authors.affiliation: Department of Chemistry and Biochemistry, University of Southern Mississippi, Hattiesburg, MS 39406, USA.
authors.forename: Dexter N
authors.initials: DN
authors.lastname: Dean
authors.affiliation: School of Polymers and High Performance Materials, University of Southern Mississippi, Hattiesburg, MS 39406, USA.
authors.forename: Pradipta K
authors.initials: PK
authors.lastname: Das
authors.affiliation: Department of Computer Science, Virginia Commonwealth University, Richmond, VA 23284, USA.
authors.forename: Pratip
authors.initials: P
authors.lastname: Rana
authors.affiliation: Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Franklin
authors.initials: F
authors.lastname: Burg
authors.affiliation: Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Yona
authors.initials: Y
authors.lastname: Levites
authors.affiliation: School of Polymers and High Performance Materials, University of Southern Mississippi, Hattiesburg, MS 39406, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Morgan
authors.affiliation: Department of Computer Science, Virginia Commonwealth University, Richmond, VA 23284, USA.
authors.forename: Preetam
authors.initials: P
authors.lastname: Ghosh
authors.affiliation: Department of Chemistry and Biochemistry, University of Southern Mississippi, Hattiesburg, MS 39406, USA.
authors.forename: Vijayaraghavan
authors.initials: V
authors.lastname: Rangachari
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000686:Amyloidosis / Q000378:metabolism / Q000473:pathology; D000818:Animals; D051379:Mice; D008822:Mice, Transgenic; D066329:Protein Aggregates; D066263:Protein Aggregation, Pathological; D055503:Protein Multimerization
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D066329:Protein Aggregates