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Immunotherapy to improve cognition and reduce pathological species in an Alzheimer's disease mouse model.


ABSTRACT: BACKGROUND:Alzheimer's disease (AD) is characterized by physiologically endogenous proteins amyloid beta (A?) and tau undergoing a conformational change and accumulating as soluble oligomers and insoluble aggregates. Tau and A? soluble oligomers, which contain extensive ?-sheet secondary structure, are thought to be the most toxic forms. The objective of this study was to determine the ability of TWF9, an anti-?-sheet conformation antibody (a?ComAb), to selectively recognize pathological A? and phosphorylated tau in AD human tissue compared with cognitively normal age-matched controls and to improve the performance of old 3xTg-AD mice with advanced pathology in behavioral testing after acute treatment with TWF9. METHODS:In this study, we used immunohistochemistry, immunoprecipitation, and enzyme-linked immunosorbent assay (ELISA) to characterize TWF9 specificity. We further assessed cognitive performance in old (18-22 months) 3xTg-AD mice using both a Barnes maze and novel object recognition after intraperitoneal administration of TWF9 (4 mg/kg) biweekly for 2 weeks before the start of behavioral testing. Injections continued for the duration of the behavioral testing, which lasted 2 weeks. RESULTS:Histological analysis of TWF9 in formalin-fixed paraffin-embedded human control and AD (ABC score: A3B3C3) brain tissue revealed preferential cytoplasmic immunoreactivity in neurons in the AD tissue compared with controls (p?

SUBMITTER: Herline K 

PROVIDER: S-EPMC6006698 | BioStudies | 2018-01-01

REPOSITORIES: biostudies

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