Articles: apolipoproteins-e.
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Journal of neurotrauma · Jul 2007
COG1410, a novel apolipoprotein E-based peptide, improves functional recovery in a murine model of traumatic brain injury.
Traumatic brain injury (TBI) is a silent epidemic affecting approximately 1.4 million Americans annually, at an estimated annual cost of $60 billion in the United States alone. Despite an increased understanding of the pathophysiology of closed head injury, there remains no pharmacological intervention proven to improve functional outcomes in this setting. Currently, the existing standard of care for TBI consists primarily of supportive measures. ⋯ This was associated with a significant attenuation of microglial activation and neuronal death in the hippocampus, the neuroanatomical substrate for learning and memory. Rationally derived apoE mimetic peptides have been demonstrated to exert neuroprotective and anti-inflammatory effects in vitro and in clinically relevant models of brain injury. This represents a novel therapeutic strategy in the treatment of TBI.
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Dement Geriatr Cogn Disord · Jan 2007
Cognitive impairment in Alzheimer's disease is modified by APOE genotype.
We examined whether impairment in specific cognitive domains in Alzheimer's disease (AD) differed according to APOE genotype and age at onset. ⋯ Memory was more impaired among APOE epsilon4 carriers than among noncarriers. By contrast, naming, executive functions and mental speed were more impaired among APOE epsilon4 noncarriers. This suggests that the APOE genotype modifies the clinical phenotype in terms of cognitive impairment in AD.
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J. Neurol. Neurosurg. Psychiatr. · Dec 2006
Review Meta AnalysisEffects of apolipoprotein E genotype on outcome after ischaemic stroke, intracerebral haemorrhage and subarachnoid haemorrhage.
Rodent models of acute ischaemic stroke and head injury suggest that apolipoprotein E (APOE) genotype influences neuronal repair, regeneration and survival after brain injury. Possession of an APOE epsilon4 allele is associated with poor outcome after head injury in clinical studies. APOE might therefore influence outcome after acute stroke in humans. ⋯ APOE may differentially affect outcome after the three main pathological types of stroke. Further, large studies are needed to confirm or refute these findings, and to assess the possibility of an interaction between the effects of APOE and age.
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Phosphorylcholine (PC) headgroup is one of the neoantigens exposed by LDL oxidation that can elicit an immune response. Active immunization with Streptococcus pneumoniae, which bears PC on its cell wall, reduced atherosclerosis in hypercholesterolemic mice and this effect was attributed to an immune response to PC. In this study we tested the hypothesis that passive immunization with a monoclonal anti-PC IgM antibody can be athero-protective in a murine model of native aortic and vein graft atherosclerosis. ⋯ Immunization did not affect circulating cholesterol levels. Taken together our data suggest that passive immunization with anti-PC IgM significantly reduces vein graft lesion size with less inflammatory phenotype without affecting cholesterol levels, indicating an athero-protective immune response to PC. Lack of effect on established native aortic lesions may have been due to short duration of therapy and/or reduced efficacy in established lesions as compared to evolving lesions of vein graft atherosclerosis.