Comparative Analysis of Amyloid-β Chemical Structure and Amyloid Plaque Morphology of Transgenic Mouse and Alzheimer's Disease Brains

作者: Yu-Min Kuo , Tyler A. Kokjohn , Thomas G. Beach , Lucia I. Sue , Daniel Brune

DOI: 10.1074/JBC.M007859200

关键词: Peptide sequenceMolecular biologyAmyloidGenetically modified mouseCyanogen bromideTransgeneChemistryContext (language use)BioinformaticsTrypsinChemical structure

摘要: We have undertaken an integrated chemical and morphological comparison of the amyloid-beta (Abeta) molecules amyloid plaques present in brains APP23 transgenic (tg) mice human Alzheimer's disease (AD) patients. Despite apparent overall structural resemblance to AD pathology, our detailed analyses revealed that although characteristic contain cores are highly resistant physical disruption, tg produced were completely soluble buffers containing SDS. Abeta alterations account for extreme stability plaque core amyloid. The corresponding lack post-translational modifications such as N-terminal degradation, isomerization, racemization, pyroglutamyl formation, oxidation, covalently linked dimers mouse provides explanation differences solubility between plaques. hypothesize either insufficient time is available or complex species-specific environment not precisely replicated mice. appraisal therapeutic agents protocols these animal models must be judged context complete equivalence lesions.

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