{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T19:14:44Z","timestamp":1759778084863,"version":"3.40.4"},"reference-count":11,"publisher":"S. Karger AG","issue":"1-4","license":[{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurodegener Dis"],"published-print":{"date-parts":[[2012]]},"abstract":"<jats:p>&lt;i&gt;Background\/Aims:&lt;\/i&gt; Retrospective cohort studies have suggested that statin users have a lower prevalence of dementia. On the other hand, a randomized controlled study failed to show beneficial effects on the cognitive decline in Alzheimer\u2019s disease (AD). However, a prospective cohort study demonstrated that users of statins had a lower incidence of AD. One possible interpretation might be that statins could prevent or delay the onset of AD, but not slow cognitive decline once the disease has set in. Given that statins could prevent or delay the onset of AD, what is the responsible mechanism? &lt;i&gt;Methods:&lt;\/i&gt; We investigated the effect of fluvastatin on A\u03b2 metabolism at a clinically relevant dose in mice. &lt;i&gt;Results:&lt;\/i&gt; Fluvastatin reduced the brain A\u03b2 level by increased trafficking of the carboxyl terminal fragment of the amyloid precursor protein (APP-CTF), which was mediated by inhibition of protein isoprenylation. Moreover, the statin reduced the brain A\u03b2 level through enhanced A\u03b2 clearance mediated by upregulation of low-density lipoprotein receptor-related protein 1 (LRP-1) expression. The statin increased LRP-1 expression, mediated by inhibition of protein isoprenylation. &lt;i&gt;Conclusion:&lt;\/i&gt; Statins might prevent the onset of AD through reduced A\u03b2 production by enhancement of APP-CTF degradation and\/or upregulation of A\u03b2 clearance. We also showed that promotion of APP-CTF degradation and upregulation of A\u03b2 clearance could be modified by a drug, suggesting possible mechanistic targets for disease-modifying drugs.<\/jats:p>","DOI":"10.1159\/000334534","type":"journal-article","created":{"date-parts":[[2012,2,1]],"date-time":"2012-02-01T08:41:11Z","timestamp":1328085671000},"page":"305-308","source":"Crossref","is-referenced-by-count":7,"title":["Dual Effects of Statins on A\u03b2 Metabolism: Upregulation of the Degradation of APP-CTF and A\u03b2 Clearance"],"prefix":"10.1159","volume":"10","author":[{"given":"Naoyuki","family":"Sato","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuru","family":"Shinohara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromi","family":"Rakugi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryuichi","family":"Morishita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2012,2,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016%2FS0140-6736%2800%2903155-X"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1001%2Farchneur.57.10.1439"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1212%2FWNL.0b013e3181d6476a"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1136%2Fjnnp.2008.150433"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1073%2Fpnas.081620098"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1385%2FNMM%3A8%3A3%3A319"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1074%2Fjbc.M702640200"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.neurobiolaging.2008.09.004"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1016%2FS0896-6273%2800%2980974-5"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1074%2Fjbc.M110.102277"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1073%2Fpnas.94.24.13287"}],"container-title":["Neurodegenerative Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/334534","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/334534","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T18:48:50Z","timestamp":1745434130000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000334534"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012]]},"references-count":11,"journal-issue":{"issue":"1-4","published-online":{"date-parts":[[2012,4,1]]},"published-print":{"date-parts":[[2012,4,19]]}},"URL":"https:\/\/doi.org\/10.1159\/000334534","archive":["Portico"],"relation":{},"ISSN":["1660-2854","1660-2862"],"issn-type":[{"type":"print","value":"1660-2854"},{"type":"electronic","value":"1660-2862"}],"subject":[],"published":{"date-parts":[[2012]]}}}