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- W2793413710 abstract "Alzheimer's disease (AD) is a devastating neurological disorder that still lacks an effective treatment, and this has stimulated an intense pursuit of disease-modifying therapeutics. Given the increasingly recognized link between AD and defective brain insulin signaling, we investigated the actions of liraglutide, a glucagon-like peptide-1 (GLP-1) analog marketed for treatment of type 2 diabetes, in experimental models of AD. Insulin receptor pathology is an important feature of AD brains that impairs the neuroprotective actions of central insulin signaling. Here, we show that liraglutide prevented the loss of brain insulin receptors and synapses, and reversed memory impairment induced by AD-linked amyloid-β oligomers (AβOs) in mice. Using hippocampal neuronal cultures, we determined that the mechanism of neuroprotection by liraglutide involves activation of the PKA signaling pathway. Infusion of AβOs into the lateral cerebral ventricle of non-human primates (NHPs) led to marked loss of insulin receptors and synapses in brain regions related to memory. Systemic treatment of NHPs with liraglutide provided partial protection, decreasing AD-related insulin receptor, synaptic, and tau pathology in specific brain regions. Synapse damage and elimination are amongst the earliest known pathological changes and the best correlates of memory impairment in AD. The results illuminate mechanisms of neuroprotection by liraglutide, and indicate that GLP-1 receptor activation may be harnessed to protect brain insulin receptors and synapses in AD. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland." @default.
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- W2793413710 date "2018-04-02" @default.
- W2793413710 modified "2023-10-15" @default.
- W2793413710 title "The diabetes drug liraglutide reverses cognitive impairment in mice and attenuates insulin receptor and synaptic pathology in a non-human primate model of Alzheimer's disease" @default.
- W2793413710 cites W15033880 @default.
- W2793413710 cites W1515929023 @default.
- W2793413710 cites W1519363809 @default.
- W2793413710 cites W1527910050 @default.
- W2793413710 cites W1589427638 @default.
- W2793413710 cites W162803433 @default.
- W2793413710 cites W1649091845 @default.
- W2793413710 cites W1819107323 @default.
- W2793413710 cites W1867017208 @default.
- W2793413710 cites W1965993201 @default.
- W2793413710 cites W1970164987 @default.
- W2793413710 cites W1971095698 @default.
- W2793413710 cites W1972609075 @default.
- W2793413710 cites W1976602187 @default.
- W2793413710 cites W1981127983 @default.
- W2793413710 cites W1981691898 @default.
- W2793413710 cites W1982795519 @default.
- W2793413710 cites W1984652813 @default.
- W2793413710 cites W1985305554 @default.
- W2793413710 cites W1986295281 @default.
- W2793413710 cites W1990752558 @default.
- W2793413710 cites W1991194098 @default.
- W2793413710 cites W1993019632 @default.
- W2793413710 cites W1995762768 @default.
- W2793413710 cites W2007265598 @default.
- W2793413710 cites W2014526423 @default.
- W2793413710 cites W2016932677 @default.
- W2793413710 cites W2017807856 @default.
- W2793413710 cites W2020486984 @default.
- W2793413710 cites W2022847635 @default.
- W2793413710 cites W2029181104 @default.
- W2793413710 cites W2029549266 @default.
- W2793413710 cites W2030198351 @default.
- W2793413710 cites W2030270894 @default.
- W2793413710 cites W2034632760 @default.
- W2793413710 cites W2040721710 @default.
- W2793413710 cites W2042751066 @default.
- W2793413710 cites W2043381283 @default.
- W2793413710 cites W2050643229 @default.
- W2793413710 cites W2051532765 @default.
- W2793413710 cites W2051993731 @default.
- W2793413710 cites W2053665966 @default.
- W2793413710 cites W2054687207 @default.
- W2793413710 cites W2057154465 @default.
- W2793413710 cites W2059947944 @default.
- W2793413710 cites W2060170946 @default.
- W2793413710 cites W2060851420 @default.
- W2793413710 cites W2066011396 @default.
- W2793413710 cites W2066694751 @default.
- W2793413710 cites W2067430815 @default.
- W2793413710 cites W2069381818 @default.
- W2793413710 cites W2075236217 @default.
- W2793413710 cites W2077569942 @default.
- W2793413710 cites W2078613171 @default.
- W2793413710 cites W2082151254 @default.
- W2793413710 cites W2082429191 @default.
- W2793413710 cites W2083553075 @default.
- W2793413710 cites W2097335530 @default.
- W2793413710 cites W2097649283 @default.
- W2793413710 cites W2098622411 @default.
- W2793413710 cites W2106339546 @default.
- W2793413710 cites W2106781151 @default.
- W2793413710 cites W2109093140 @default.
- W2793413710 cites W2109727228 @default.
- W2793413710 cites W2111242088 @default.
- W2793413710 cites W2111749961 @default.
- W2793413710 cites W2124852816 @default.
- W2793413710 cites W2135148756 @default.
- W2793413710 cites W2140666083 @default.
- W2793413710 cites W2144486959 @default.
- W2793413710 cites W2144531560 @default.
- W2793413710 cites W2145577892 @default.
- W2793413710 cites W2146534889 @default.
- W2793413710 cites W2147654688 @default.