title: Aβ41 Aggregates More Like Aβ40 than Like Aβ42: In Silico and in Vitro Study.
abstract: Formation of intracellular plaques and small oligomeric species of amyloid β (Aβ) peptides inside neurons is a hallmark of Alzheimer's disease. The most abundant Aβ species in the brain are Aβ1-40 and Aβ1-42, which are composed, respectively, of 40 and 42 residues. Aβ1-42 differs from Aβ1-40 only in two residues, Ile41 and Ala42, yet it shows remarkably faster aggregation and greater neurotoxicity than Aβ1-40. Thus, it is crucial to understand the relative contributions of Ile41 and Ala42 to these distinct behaviors. To achieve this, secondary structures of the Aβ1-41 monomer, which contribute to aggregation propensity, were studied by all-atom molecular dynamics simulation in an implicit solvent and compared to those of Aβ1-40 and Aβ1-42. We find that the secondary structure populations of Aβ1-41 are much closer to those of Aβ1-40 than to those of Aβ1-42, suggesting that Aβ1-41 and Aβ1-40 are likely to have similar aggregation properties. This prediction was confirmed through a thioflavin-T aggregation assay. Thus, our finding indicates that the hydrophobic residue at position 42 is the major contributor to the increased fibril formation rates and consequently neurotoxicity of Aβ peptides.
authors.affiliation: Institute for Computational Science and Technology , SBI Building, Quang Trung Software City, Tan Chanh Hiep Ward, District 12, Ho Chi Minh City, Vietnam.|Department of Applied Physics, Faculty of Applied Science, Ho Chi Minh City University of Technology - VNU HCM , 268 Ly Thuong Kiet Street, District 10, Ho Chi Minh City, Vietnam.
authors.forename: Hoang Linh
authors.initials: HL
authors.lastname: Nguyen
authors.affiliation: Institute for Computational Science and Technology , SBI Building, Quang Trung Software City, Tan Chanh Hiep Ward, District 12, Ho Chi Minh City, Vietnam.|Department of Applied Physics, Faculty of Applied Science, Ho Chi Minh City University of Technology - VNU HCM , 268 Ly Thuong Kiet Street, District 10, Ho Chi Minh City, Vietnam.
authors.forename: Tran
authors.initials: T
authors.lastname: Thi Minh Thu
authors.affiliation: Institute for Computational Science and Technology , SBI Building, Quang Trung Software City, Tan Chanh Hiep Ward, District 12, Ho Chi Minh City, Vietnam.
authors.forename: Phan Minh
authors.initials: PM
authors.lastname: Truong
authors.affiliation: Institute for Computational Science and Technology , SBI Building, Quang Trung Software City, Tan Chanh Hiep Ward, District 12, Ho Chi Minh City, Vietnam.
authors.forename: Pham Dang
authors.initials: PD
authors.lastname: Lan
authors.affiliation: Institute of Physics, Polish Academy of Sciences , Al. Lotnikow 32/46, 02-668 Warsaw, Poland.
authors.forename: Viet Hoang
authors.initials: VH
authors.lastname: Man
authors.affiliation: Laboratoire de Biochimie Theorique, UPR 9080 CNRS, IBPC, Universite Paris 7, 13 rue Pierre et Marie Curie, 75005 Paris, France.
authors.forename: Phuong H
authors.initials: PH
authors.lastname: Nguyen
authors.affiliation: Department of Applied Physics, Faculty of Applied Science, Ho Chi Minh City University of Technology - VNU HCM , 268 Ly Thuong Kiet Street, District 10, Ho Chi Minh City, Vietnam.
authors.forename: Ly Anh
authors.initials: LA
authors.lastname: Tu
authors.affiliation: Department of Medicine, MacKay Medical College , New Taipei City 252, Taiwan.
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Institute of Physics, Polish Academy of Sciences , Al. Lotnikow 32/46, 02-668 Warsaw, Poland.
authors.forename: Mai Suan
authors.initials: MS
authors.lastname: Li
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D066329:Protein Aggregates; D017433:Protein Structure, Secondary; D013816:Thermodynamics
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D066329:Protein Aggregates; C078592:amyloid beta-protein (1-40); C497285:amyloid beta-protein (1-41); C075222:amyloid beta-protein (1-42)