{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T04:04:34Z","timestamp":1791777874084,"version":"4.3.4"},"reference-count":60,"publisher":"Rockefeller University Press","issue":"13","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,12,17]]},"abstract":"<jats:p>There is extensive evidence that cholesterol and membrane lipids play a key role in Alzheimer disease (AD) pathogenesis. Cyclodextrins (CD) are cyclic oligosaccharide compounds widely used to bind cholesterol. Because CD exerts significant beneficial effects in Niemann-Pick type C disease, which shares neuropathological features with AD, we examined the effects of hydroxypropyl-\u03b2-CD (HP-\u03b2-CD) in cell and mouse models of AD. Cell membrane cholesterol accumulation was detected in N2a cells overexpressing Swedish mutant APP (SwN2a), and the level of membrane cholesterol was reduced by HP-\u03b2-CD treatment. HP-\u03b2-CD dramatically lowered the levels of A\u03b242 in SwN2a cells, and the effects were persistent for 24 h after withdrawal. 4 mo of subcutaneous HP-\u03b2-CD administration significantly improved spatial learning and memory deficits in Tg19959 mice, diminished A\u03b2 plaque deposition, and reduced tau immunoreactive dystrophic neurites. HP-\u03b2-CD lowered levels of A\u03b242 in part by reducing \u03b2 cleavage of the APP protein, and it also up-regulated the expression of genes involved in cholesterol transport and A\u03b2 clearance. This is the first study to show neuroprotective effects of HP-\u03b2-CD in a transgenic mouse model of AD, both by reducing A\u03b2 production and enhancing clearance mechanisms, which suggests a novel therapeutic strategy for AD.<\/jats:p>","DOI":"10.1084\/jem.20121239","type":"journal-article","created":{"date-parts":[[2012,12,4]],"date-time":"2012-12-04T08:40:46Z","timestamp":1354610446000},"page":"2501-2513","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":147,"title":["Neuroprotection by cyclodextrin in cell and mouse models of Alzheimer disease"],"prefix":"10.1084","volume":"209","author":[{"given":"Jiaqi","family":"Yao","sequence":"first","affiliation":[{"name":"Department of Neurology and Neuroscience 1 and 2"},{"name":"Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neuroscience 1 and 2"},{"name":"Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noel Y.","family":"Calingasan","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neuroscience 1 and 2"},{"name":"Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina H.","family":"Pipalia","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neuroscience 1 and 2"},{"name":"Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neuroscience 1 and 2"},{"name":"Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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