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P4‐318: Amyloid beta (AB) nanoparticles employed to study intracellular tau protein interaction
Author(s) -
Hasan Syed,
Hall Garth
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.09.063
Subject(s) - endosome , microvesicles , exosome , colocalization , secretion , microbiology and biotechnology , tau protein , intracellular , vesicle , chemistry , amyloid precursor protein , amyloid beta , gene isoform , amyloid (mycology) , biophysics , biochemistry , alzheimer's disease , biology , medicine , pathology , peptide , microrna , inorganic chemistry , disease , membrane , gene
research on the molecular biology of AD. While the conformation adopted by Aß within these aggregates is not known, a ß-hairpin conformation is known to be accessible to monomeric Aß. The ß-hairpin is for instance observed in a complex with Affibody binding protein. Methods: To test the hypothesis that the ß-hairpin is a building block of toxic oligomers, we have engineered a double-cysteine mutant of Aß (called AßCC) in which the ß-hairpin conformation is stabilized by an intramolecular disulfide bond. AßCC oligomers were characterized to determine if they represent a stable model of wild type neurotoxic aggregates. Results: Aß40CC and Aß42CC form stable protofibrils, but are unable to convert into amyloid fibrils. Biochemical and biophysical experiments and assays with conformation-specific antibodies used to detect Aß aggregates in vivo indicate that the wild-type oligomer structure is preserved and stabilized in AßCC oligomers. Stable oligomers are potent inducers of neuronal apoptosis. Conclusions: Stable neurotoxic AßCC oligomers/protofibrils might facilitate studies of their structure and role in the pathogenesis of AD. Stable protofibril preparations might potentially also be used for therapy development based on active or passive immunization.