| First Author | Yao J | Year | 2012 |
| Journal | J Exp Med | Volume | 209 |
| Issue | 13 | Pages | 2501-13 |
| PubMed ID | 23209315 | Mgi Jnum | J:194631 |
| Mgi Id | MGI:5474426 | Doi | 10.1084/jem.20121239 |
| Citation | Yao J, et al. (2012) Neuroprotection by cyclodextrin in cell and mouse models of Alzheimer disease. J Exp Med 209(13):2501-13 |
| abstractText | 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-beta-CD (HP-beta-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-beta-CD treatment. HP-beta-CD dramatically lowered the levels of Abeta42 in SwN2a cells, and the effects were persistent for 24 h after withdrawal. 4 mo of subcutaneous HP-beta-CD administration significantly improved spatial learning and memory deficits in Tg19959 mice, diminished Abeta plaque deposition, and reduced tau immunoreactive dystrophic neurites. HP-beta-CD lowered levels of Abeta42 in part by reducing beta cleavage of the APP protein, and it also up-regulated the expression of genes involved in cholesterol transport and Abeta clearance. This is the first study to show neuroprotective effects of HP-beta-CD in a transgenic mouse model of AD, both by reducing Abeta production and enhancing clearance mechanisms, which suggests a novel therapeutic strategy for AD. |
