Point mutations in Aβ induce polymorphic aggregates at liquid/solid interfaces.
A pathological hallmark of Alzheimer's disease (AD), a late onset neurodegenerative disease, is the development of neuritic amyloid plaques, composed predominantly of aggregates of the β-amyloid (Aβ) peptide. It has been demonstrated that Aβ can aggregate into a variety of polymorphic aggregate structures under different chemical environments, and a potentially important environmental factor in dictating aggregate structure is the presence of surfaces. There are also several mutations clustered around the central hydrophobic core of Aβ (E22G Arctic mutation, E22K Italian mutation, D23N Iowa mutation, and A21G Flemish mutation). These mutations are associated with hereditary diseases ranging from almost pure cerebral amyloid angiopathy (CAA) to typical Alzheimer's disease pathology. The goal of this study was to determine how these mutations influence the morphology of Aβ aggregates under free solution conditions and at an anionic surface/liquid interface. While the rate of formation of specific aggregates was altered by mutations in Aβ under free solution conditions, the respective aggregate morphologies were similar. However, aggregation occurring directly on a negatively charged mica surface resulted in distinct aggregate morphologies formed by different mutant forms of Aβ. These studies provide insight into the potential role anionic surfaces play in dictating the formation of Aβ polymorphic aggregate structures.
The C. Eugene Bennett Department of Chemistry, West Virginia University, 217 Clark Hall, P.O. Box 6045, Morgantown, West Virginia 26506, United States.
Elizabeth A
EA
Yates
Elena M
EM
Cucco
Justin
J
Legleiter
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000235:genetics*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000235:genetics*; D013500:Surface Tension
D016229:Amyloid beta-Peptides