{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:09:06Z","timestamp":1791911346341,"version":"4.3.4"},"reference-count":48,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2016,7,22]],"date-time":"2016-07-22T00:00:00Z","timestamp":1469145600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:p>Apolipoprotein E \u025b4 allele is a common susceptibility gene for late-onset Alzheimer's disease. Brain vascular and metabolic deficits can occur in cognitively normal apolipoprotein E \u025b4 carriers decades before the onset of Alzheimer's disease. The goal of this study was to determine whether early intervention using rapamycin could restore neurovascular and neurometabolic functions, and thus impede pathological progression of Alzheimer's disease-like symptoms in pre-symptomatic Apolipoprotein E \u025b4 transgenic mice. Using in\u00a0vivo, multimodal neuroimaging, we found that apolipoprotein E \u025b4 mice treated with rapamycin had restored cerebral blood flow, blood\u2013brain barrier integrity and glucose metabolism, compared to age- and gender-matched wild-type controls. The preserved vasculature and metabolism were associated with amelioration of incipient learning deficits. We also found that rapamycin restored the levels of the proinflammatory cyclophilin A in vasculature, which may contribute to the preservation of cerebrovascular function in the apolipoprotein E \u025b4 transgenics. Our results show that rapamycin improves functional outcomes in this mouse model and may have potential as an effective intervention to block progression of vascular, metabolic and early cognitive deficits in human Apolipoprotein E \u025b4 carriers. As rapamycin is FDA-approved and neuroimaging is readily used in humans, the results of the present study may provide the basis for future Alzheimer's disease intervention studies in human subjects.<\/jats:p>","DOI":"10.1177\/0271678x15621575","type":"journal-article","created":{"date-parts":[[2015,12,31]],"date-time":"2015-12-31T21:19:53Z","timestamp":1451596793000},"page":"217-226","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":149,"title":["Rapamycin rescues vascular, metabolic and learning deficits in apolipoprotein E4 transgenic mice with pre-symptomatic Alzheimer\u2019s disease"],"prefix":"10.1177","volume":"37","author":[{"given":"Ai-Ling","family":"Lin","sequence":"first","affiliation":[{"name":"Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA"},{"name":"Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA"},{"name":"Department of 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