The unfolded protein response is activated in the olfactory system in Alzheimer's disease.

Show simple item record Murray, Helen en Dieriks, Birger en Swanson, Molly en Anekal, Praju Vikas en Turner, Clinton en Faull, Richard en Belluscio, Leonardo en Koretsky, Alan en Curtis, Maurice en 2020-08-17T01:41:13Z en 2020-07-14 en
dc.identifier.citation Acta neuropathologica communications 8(1):109 14 Jul 2020 en
dc.identifier.issn 2051-5960 en
dc.identifier.uri en
dc.description.abstract Olfactory dysfunction is an early and prevalent symptom of Alzheimer's disease (AD) and the olfactory bulb is a nexus of beta-amyloid plaque and tau neurofibrillary tangle (NFT) pathology during early AD progression. To mitigate the accumulation of misfolded proteins, an endoplasmic reticulum stress response called the unfolded protein response (UPR) occurs in the AD hippocampus. However, chronic UPR activation can lead to apoptosis and the upregulation of beta-amyloid and tau production. Therefore, UPR activation in the olfactory system could be one of the first changes in AD. In this study, we investigated whether two proteins that signal UPR activation are expressed in the olfactory system of AD cases with low or high amounts of aggregate pathology. We used immunohistochemistry to label two markers of UPR activation (p-PERK and p-eIF2α) concomitantly with neuronal markers (NeuN and PGP9.5) and pathology markers (beta-amyloid and tau) in the olfactory bulb, piriform cortex, entorhinal cortex and the CA1 region of the hippocampus in AD and normal cases. We show that UPR activation, as indicated by p-PERK and p-eIF2α expression, is significantly increased throughout the olfactory system in AD cases with low (Braak stage III-IV) and high-level (Braak stage V-VI) pathology. We further show that UPR activation occurs in the mitral cells and in the anterior olfactory nucleus of the olfactory bulb where tau and amyloid pathology is abundant. However, UPR activation is not present in neurons when they contain NFTs and only rarely occurs in neurons containing diffuse tau aggregates. We conclude that UPR activation is prevalent in all regions of the olfactory system and support previous findings suggesting that UPR activation likely precedes NFT formation. Our data indicate that chronic UPR activation in the olfactory system might contribute to the olfactory dysfunction that occurs early in the pathogenesis of AD. en
dc.format.medium Electronic en
dc.language eng en
dc.relation.ispartofseries Acta Neuropathologica Communications en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri en
dc.rights.uri en
dc.title The unfolded protein response is activated in the olfactory system in Alzheimer's disease. en
dc.type Journal Article en
dc.identifier.doi 10.1186/s40478-020-00986-7 en
pubs.issue 1 en
pubs.begin-page 109 en
pubs.volume 8 en
dc.rights.holder Copyright: The authors en
pubs.publication-status Published en
dc.rights.accessrights en
pubs.subtype research-article en
pubs.subtype Journal Article en
pubs.elements-id 809359 en Medical and Health Sciences en Medical Sciences en Anatomy and Medical Imaging en Science en Biological Sciences en
dc.identifier.eissn 2051-5960 en
pubs.record-created-at-source-date 2020-07-16 en
pubs.dimensions-id 32665027 en

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