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

Autor: Krystal Herline, Frances Prelli, Pankaj Mehta, Claire MacMurray, Fernando Goñi, Thomas Wisniewski
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Alzheimer’s Research & Therapy, Vol 10, Iss 1, Pp 1-18 (2018)
Druh dokumentu: article
ISSN: 1758-9193
DOI: 10.1186/s13195-018-0384-9
Popis: Abstract Background Alzheimer’s disease (AD) is characterized by physiologically endogenous proteins amyloid beta (Aβ) and tau undergoing a conformational change and accumulating as soluble oligomers and insoluble aggregates. Tau and Aβ soluble oligomers, which contain extensive β-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-β-sheet conformation antibody (aβComAb), to selectively recognize pathological Aβ 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
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