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An electrostatic cluster guides Aβ40 fibril formation in sporadic and Dutch-type cerebral amyloid angiopathy.
J Struct Biol
June 2024
Center for Structural Biology, Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794-5215, United States.
Cerebral amyloid angiopathy (CAA) is associated with the accumulation of fibrillar Aβ peptides upon and within the cerebral vasculature, which leads to loss of vascular integrity and contributes to disease progression in Alzheimer's disease (AD). We investigate the structure of human-derived Aβ40 fibrils obtained from patients diagnosed with sporadic or familial Dutch-type (E22Q) CAA. Using cryo-EM, two primary structures are identified containing elements that have not been observed in in vitro Aβ40 fibril structures.
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