Postsynaptic dysfunction is associated with spatial and object recognition memory loss in a natural model of Alzheimer's disease.

Abstract : Alzheimer's disease (AD) is an age-related neurodegenerative disorder associated with progressive memory loss, severe dementia, and hallmark neuropathological markers, such as deposition of amyloid-β (Aβ) peptides in senile plaques and accumulation of hyperphosphorylated tau proteins in neurofibrillary tangles. Recent evidence obtained from transgenic mouse models suggests that soluble, nonfibrillar Aβ oligomers may induce synaptic failure early in AD. Despite their undoubted value, these transgenic models rely on genetic manipulations that represent the inherited and familial, but not the most abundant, sporadic form of AD. A nontransgenic animal model that still develops hallmarks of AD would be an important step toward understanding how sporadic AD is initiated. Here we show that starting between 12 and 36 mo of age, the rodent Octodon degus naturally develops neuropathological signs of AD, such as accumulation of Aβ oligomers and phosphorylated tau proteins. Moreover, age-related changes in Aβ oligomers and tau phosphorylation levels are correlated with decreases in spatial and object recognition memory, postsynaptic function, and synaptic plasticity. These findings validate O. degus as a suitable natural model for studying how sporadic AD may be initiated.
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Alvaro O Ardiles, Cheril C Tapia-Rojas, Madhuchhanda Mandal, Frédéric Alexandre, Alfredo Kirkwood, et al.. Postsynaptic dysfunction is associated with spatial and object recognition memory loss in a natural model of Alzheimer's disease.. Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2012, 109 (34), pp.13835-40. ⟨10.1073/pnas.1201209109⟩. ⟨hal-00746807⟩

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