{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T08:51:46Z","timestamp":1785487906069,"version":"3.56.0"},"reference-count":60,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T00:00:00Z","timestamp":1724976000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010146","name":"Alzheimer Forschung Initiative","doi-asserted-by":"publisher","award":["12851"],"award-info":[{"award-number":["12851"]}],"id":[{"id":"10.13039\/100010146","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010146","name":"Alzheimer Forschung Initiative","doi-asserted-by":"publisher","award":["20026"],"award-info":[{"award-number":["20026"]}],"id":[{"id":"10.13039\/100010146","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Cellular prion protein (PrP<jats:sup>C<\/jats:sup>) was implicated in amyloid beta (A\u03b2)\u2010induced toxicity in Alzheimer's disease (AD), but the precise molecular mechanisms involved in this process are\u00a0unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Double transgenic mice were generated by crossing Prnp knockout (KO) with 5xFAD mice, and light\u2010sheet microscopy was used for whole brain tissue analyses. PrP<jats:sup>C<\/jats:sup>\u2010overexpressing cells were developed for in vitro studies, and microscopy was used to assess co\u2010localization of proteins of interest. Surface\u2010plasmon resonance (SPR) was used to investigate protein\u2010binding characteristics.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>In vivo, PrP<jats:sup>C\u00a0<\/jats:sup>levels correlated with reduced lifespan and cognitive and motor function, and its ablation disconnected behavior deficits from A\u03b2 levels. Light\u2010sheet microscopy showed that PrP<jats:sup>C<\/jats:sup>\u00a0influenced A\u03b2\u2010plaque burden but not the distribution of those plaques. Interestingly, caveolin\u20101 (Cav\u20101) KO neurons significantly reduced intracellular A\u03b2\u2010oligomer (A\u03b2o) uptake when compared to wild\u2010type neurons.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>The findings shed new light on the relevance of intracellular A\u03b2o, suggesting that PrP<jats:sup>C<\/jats:sup>\u00a0and Cav\u20101 modulate intracellular A\u03b2 levels and\u00a0the A\u03b2\u2010plaque load.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>PrP<jats:sup>C<\/jats:sup> expression adversely affects lifespan and behavior in 5xFAD mice.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>PrP<jats:sup>C<\/jats:sup> increases A\u03b21\u201040 and A\u03b21\u201042 levels and A\u03b2\u2010plaque load in 5xFAD mice.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Cav\u20101 interacts with both PrP<jats:sup>C<\/jats:sup> and A\u03b2 peptides.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Knocking out Cav\u20101 leads to a significant reduction in intracellular A\u03b2 levels.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.14120","type":"journal-article","created":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T08:20:17Z","timestamp":1725006017000},"page":"6776-6792","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Cellular prion protein acts as mediator of amyloid beta uptake by caveolin\u20101 causing cellular dysfunctions in vitro and in vivo"],"prefix":"10.1002","volume":"20","author":[{"given":"Angela","family":"da Silva Correia","sequence":"first","affiliation":[{"name":"Department of Neurology University Medical Center and the German Center for Neurodegenerative Diseases (DZNE) Georg\u2010August University  Goettingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Department of Neurology University Medical Center and the German Center for Neurodegenerative Diseases (DZNE) Georg\u2010August University  Goettingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna\u2010Lisa","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Neurology University Medical Center and the German Center for Neurodegenerative Diseases (DZNE) Georg\u2010August University  Goettingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"da Silva Correia","sequence":"additional","affiliation":[{"name":"Department of Neurology University Medical Center and the German Center for Neurodegenerative Diseases (DZNE) Georg\u2010August University  Goettingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco L.","family":"Simonetti","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Instituto Leloir  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gesine","family":"Saher","sequence":"additional","affiliation":[{"name":"Department of Neurogenetics Max Planck Institute for Multidisciplinary Sciences  Goettingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Goya\u2010Maldonado","sequence":"additional","affiliation":[{"name":"Laboratory of Systems Neuroscience and Imaging in Psychiatry (SNIP\u2010Lab) Department of Psychiatry and Psychotherapy University Medical Center Goettingen (UMG)  Goettingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amandeep Singh","family":"Arora","sequence":"additional","affiliation":[{"name":"Texas Therapeutics Institute Brown Foundation Institute of Molecular Medicine University of Texas Health Science Center at Houston  Houston Texas 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