title: Cross-seeding between Aβ40 and Aβ42 in Alzheimer's disease.
abstract: Aβ42 is the major component of parenchymal plaques in the brain of Alzheimer's patients, while Aβ40 is the major component of cerebrovascular plaques. Since Aβ40 and Aβ42 coexist in the brain, understanding the interaction between Aβ40 and Aβ42 during their aggregation is important to delineate the molecular mechanism underlying Alzheimer's disease. Here, we present a rigorous and systematic study of the cross-seeding effects between Aβ40 and Aβ42. We show that Aβ40 fibril seeds can promote Aβ42 aggregation in a concentration-dependent manner, and vice versa. Our results also suggest that seeded aggregation and spontaneous aggregation may be two separate pathways. These findings may partly resolve conflicting observations in the literature regarding the cross-seeding effects between Aβ40 and Aβ42.
authors.affiliation: Department of Neurology, Brain Research Institute, Molecular Biology Institute, University of California, Los Angeles, CA, USA.
authors.forename: Joyce
authors.initials: J
authors.lastname: Tran
authors.affiliation: Department of Neurology, Brain Research Institute, Molecular Biology Institute, University of California, Los Angeles, CA, USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: Chang
authors.affiliation: Department of Neurology, Brain Research Institute, Molecular Biology Institute, University of California, Los Angeles, CA, USA.
authors.forename: Frederick
authors.initials: F
authors.lastname: Hsu
authors.affiliation: Department of Neurology, Brain Research Institute, Molecular Biology Institute, University of California, Los Angeles, CA, USA.
authors.forename: Hongsu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurology, Brain Research Institute, Molecular Biology Institute, University of California, Los Angeles, CA, USA.
authors.forename: Zhefeng
authors.identifier: http://orcid.org/0000-0003-1992-7255
authors.initials: Z
authors.lastname: Guo
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000682:Amyloid / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D066329:Protein Aggregates
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D066329:Protein Aggregates
keywords: Amyloid; fibrillization kinetics; protein aggregation