Articles: apolipoproteins-e.
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Sphingolipids play a very important role in cell membrane formation, signal transduction, and plasma lipoprotein metabolism, all of which may well have an impact on the development of atherosclerosis. To investigate the relationship between sphingolipid metabolism and atherosclerosis, we utilized myriocin to inhibit mouse serine palmitoyl-CoA transferase (SPT), the key enzyme for sphingolipid biosynthesis. We injected 8-week-old apoE-deficient mice with myriocin (0.3 mg/kg/every other day, intraperitoneal) for 60 days. ⋯ Total cholesterol and triglyceride demonstrated no significant changes, but there was a significant decrease in atherosclerotic lesion area (39% in root and 37% in en face assays) (p < 0.01). These results indicate that, apart from cholesterol levels, sphingolipids have an effect on atherosclerotic development and that SPT has proatherogenic properties. Thus, inhibition of SPT activity could be an alternative treatment for atherosclerosis.
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Alzheimer's disease (AD) is characterized by the aggregation and deposition of the normally soluble amyloid-beta (Abeta) peptide in the extracellular spaces of the brain as parenchymal plaques and in the walls of cerebral vessels as cerebral amyloid angiopathy (CAA). CAA is a common cause of brain hemorrhage and is found in most patients with AD. As in AD, the epsilon4 allele of the apolipoprotein E (apoE) gene (APOE) is a risk factor for CAA. ⋯ At 15 months of age, the expression of human apoE4 led to substantial CAA with very few parenchymal plaques, whereas the expression of human apoE3 resulted in almost no CAA or parenchymal plaques. Additionally, young apoE4-expressing mice had an elevated ratio of Abeta 40:42 in brain extracellular pools and a lower 40:42 ratio in CSF, suggesting that apoE4 results in altered clearance and transport of Abeta species within different brain compartments. These findings demonstrate that, once Abeta fibrillogenesis occurs, apoE4 favors the formation of CAA over parenchymal plaques and suggest that molecules or treatments that increase the ratio of Abeta 40:42 may favor the formation of CAA versus parenchymal plaques.
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J. Gerontol. A Biol. Sci. Med. Sci. · Mar 2005
Comparative StudyApolipoprotein epsilon4 allele and problems with orientation are associated with a persistent decline in cognition in community-dwelling elderly persons.
A decline in cognitive test scores in elderly persons can signal the beginning of a descent into dementia or may indicate only a short-term cognitive disturbance. It would be clinically useful to distinguish between the two outcomes and to identify characteristics of each. ⋯ Persistent cognitive decline is an infrequent occurrence in community-dwelling elderly persons. Presence of the epsilon4 allele and errors made by the subject on questions of orientation may be useful in determining whether a cognitive decline is likely to be persistent.
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Experimental neurology · Mar 2005
A novel therapeutic derived from apolipoprotein E reduces brain inflammation and improves outcome after closed head injury.
Although apolipoprotein E4 (APOE4) was initially identified as a susceptibility gene for the development of Alzheimer's disease, the presence of the APOE4 allele is also associated with poor outcome after acute brain injury. One mechanism by which apoE may influence neurological outcome is by downregulating the neuroinflammatory response. ⋯ We demonstrate that a single intravenous injection of a small peptide derived from the apoE receptor binding region crosses the blood-brain barrier and significantly improves histological and functional outcomes after traumatic brain injury (TBI). The development of an apoE-based intervention represents a novel therapeutic strategy in the management of acute brain injury.
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The possession of at least one APOE-epsilon4 allele may be linked to poor outcome in patients with predominantly severe traumatic brain injury (TBI). In mild TBI, which accounts for approximately 85% of all cases, the role of the APOE-epsilon4 allele is less clear. ⋯ No association was found between the presence of the APOE-epsilon4 allele and poor outcome across all measures. Given the homogeneous nature of our sample (mild to moderate injury severity), the uniform follow-up period (6 months) and the comprehensive markers of recovery used, our data suggest that the APOE-epsilon4 allele does not adversely impact outcome in this group of TBI patients.