{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T15:38:18Z","timestamp":1776872298404,"version":"3.51.2"},"reference-count":30,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T00:00:00Z","timestamp":1700179200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council","doi-asserted-by":"crossref","award":["MC_UU_00024\/9"],"award-info":[{"award-number":["MC_UU_00024\/9"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Leonard Wolfson Experimental Neurology Centre"},{"name":"Leonard Wolfson Experimental Neurology Centre"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Oligomers formed from monomers of the amyloid \u03b2-protein (A\u03b2) are thought to be central to the pathogenesis of Alzheimer\u2019s disease (AD). Unsurprisingly for a complex disease, current mouse models of AD fail to fully mimic the clinical disease in humans. Moreover, results obtained in a given mouse model are not always reproduced in a different model. Cellular prion protein (PrP<jats:sup>C<\/jats:sup>) is now an established receptor for A\u03b2 oligomers. However, studies of the A\u03b2-PrP<jats:sup>C<\/jats:sup> interaction in different mouse models have yielded contradictory results. Here we performed a longitudinal study assessing a range of biochemical and histological features in the commonly used J20 and APP-PS1 mouse models. Our analysis demonstrated that PrP<jats:sup>C<\/jats:sup> ablation had no effect on amyloid accumulation or oligomer production. However, we found that APP-PS1 mice had higher levels of oligomers, that these could bind to recombinant PrP<jats:sup>C<\/jats:sup>, and were recognised by the OC antibody which distinguishes parallel, in register fibrils. On the other hand, J20 mice had a lower level of A\u03b2 oligomers, which did not interact with PrP<jats:sup>C<\/jats:sup> when tested <jats:italic>in vitro<\/jats:italic> and were OC-negative. These results suggest the two mouse models produce diverse A\u03b2 assemblies that could interact with different targets, highlighting the necessity to characterise the conformation of the A\u03b2 oligomers concomitantly with the toxic cascade elicited by them. Our results provide an explanation for the apparent contradictory results found in APP-PS1 mice and the J20 mouse line in regards to A\u03b2 toxicity mediated by PrP<jats:sup>C<\/jats:sup>.<\/jats:p>","DOI":"10.1371\/journal.pone.0294465","type":"journal-article","created":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T18:24:31Z","timestamp":1700245471000},"page":"e0294465","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Two mouse models of Alzheimer\u2019s disease accumulate amyloid at different rates and have distinct A\u03b2 oligomer profiles unaltered by ablation of cellular prion protein"],"prefix":"10.1371","volume":"18","author":[{"given":"Silvia A.","family":"Purro","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Farmer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Noble","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire J.","family":"Sarell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan","family":"Powell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Yip","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren","family":"Giggins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leila","family":"Zakka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David X.","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Farrow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew J.","family":"Nicoll","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominic","family":"Walsh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Collinge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,11,17]]},"reference":[{"issue":"10","key":"pone.0294465.ref001","doi-asserted-by":"crossref","first-page":"4012","DOI":"10.1073\/pnas.0811698106","article-title":"Oligomeric amyloid beta associates with postsynaptic densities and correlates with excitatory synapse loss near senile plaques","volume":"106","author":"RM Koffie","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7","key":"pone.0294465.ref002","doi-asserted-by":"crossref","first-page":"3174","DOI":"10.1074\/jbc.R115.702704","article-title":"Amyloid-beta receptors: the good, the bad and the prion protein","volume":"291","author":"HH Jarosz-Griffiths","year":"2015","journal-title":"J Biol chem"},{"issue":"4","key":"pone.0294465.ref003","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.biopsych.2017.11.020","article-title":"Prion Protein as a Toxic Acceptor of Amyloid-beta Oligomers","volume":"83","author":"SA Purro","year":"2018","journal-title":"Biol Psychiatry"},{"issue":"15","key":"pone.0294465.ref004","doi-asserted-by":"crossref","first-page":"6042","DOI":"10.1074\/jbc.RA118.006252","article-title":"Systematic and standardized comparison of reported amyloid-beta receptors for sufficiency, affinity, and Alzheimer\u2019s disease relevance","volume":"294","author":"LM Smith","year":"2019","journal-title":"J Biol Chem"},{"key":"pone.0294465.ref005","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/ncomms1341","article-title":"Interaction between prion protein and toxic amyloid beta assemblies can be therapeutically targeted at multiple sites","volume":"2","author":"DB Freir","year":"2011","journal-title":"Nat Commun"},{"issue":"18","key":"pone.0294465.ref006","doi-asserted-by":"crossref","first-page":"6140","DOI":"10.1523\/JNEUROSCI.3526-13.2014","article-title":"Peripheral Administration of a Humanized Anti-PrP Antibody Blocks Alzheimer\u2019s Disease Abeta Synaptotoxicity","volume":"34","author":"I Klyubin","year":"2014","journal-title":"J Neurosci"},{"key":"pone.0294465.ref007","doi-asserted-by":"crossref","first-page":"2416","DOI":"10.1038\/ncomms3416","article-title":"Amyloid-beta nanotubes are associated with prion protein-dependent synaptotoxicity.","volume":"4","author":"AJ Nicoll","year":"2013","journal-title":"Nat Commun"},{"issue":"5","key":"pone.0294465.ref008","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/j.neuron.2013.06.036","article-title":"Metabotropic glutamate receptor 5 is a coreceptor for Alzheimer abeta oligomer bound to cellular prion protein","volume":"79","author":"JW 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Collinge","year":"2016","journal-title":"Nature"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0294465","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T18:24:56Z","timestamp":1700245496000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0294465"}},"subtitle":[],"editor":[{"given":"Human","family":"Rezaei","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2023,11,17]]},"references-count":30,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,11,17]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0294465","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,17]]}}}