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- Title
Systemic treatment with liver X receptor agonists raises apolipoprotein E, cholesterol, and amyloid-β peptides in the cerebral spinal fluid of rats.
- Authors
Suon, Sokreine; Jie Zhao; Villarreal, Stephanie A.; Anumula, Nikesh; Mali Liu; Carangia, Linda M.; Renger, John J.; Zerbinatti, Celina V.
- Abstract
Background: Apolipoprotein E (apoE) is a major cholesterol transport protein found in association with brain amyloid from Alzheimer's disease (AD) patients and the e4 allele of apoE is a genetic risk factor for AD. Previous studies have shown that apoE forms a stAβle complex with amyloid b (Aβ) peptides in vitro and that the state of apoE lipidation influences the fate of brain Aβ, i.e., lipid poor apoE promotes Aβ aggregation/deposition while fully lipidated apoE favors Aβ degradation/clearance. In the brain, apoE levels and apoE lipidation are regulated by the liver X receptors (LXRs). Results: We investigated the hypothesis that increased apoE levels and lipidation induced by LXR agonists facilitates Aβ efflux from the brain to the cerebral spinal fluid (CSF). We also examined if the brain expression of major apoE receptors potentially involved in apoE-mediated Aβ clearance was altered by LXR agonists. ApoE, cholesterol, Aβ40, and Aβ42 levels were all significantly elevated in the CSF of rats after only 3 days of treatment with LXR agonists. A significant reduction in soluble brain Aβ40 levels was also detected after 6 days of LXR agonist treatment. Conclusions: Our novel findings suggest that central Aβ lowering caused by LXR agonists appears to involve an apoE/cholesterol-mediated transport of Aβ to the CSF and that differences between the apoE isoforms in mediating this clearance pathway may explain why individuals carrying one or two copies of APOE ϵ4 have increased risk for AD.
- Subjects
APOLIPOPROTEIN E; ALZHEIMER'S patients; DISEASES in older people; CARRIER proteins; CEREBROSPINAL fluid
- Publication
Molecular Neurodegeneration, 2010, Vol 5, p44
- ISSN
1750-1326
- Publication type
Article
- DOI
10.1186/1750-1326-5-44