PURPOSE Age-related macular degeneration (AMD) is a leading cause of severe visual impairment in older adults worldwide. Cigarette smoking is one of the most consistently identified environmental risk factors for the disease. Several studies have implicated the apolipoprotein E (APOE) gene as modulating AMD risk. The purpose of this study was to investigate whether APOE genotypes modify the smo...

Atorvastatin, a synthetic HMG-CoA reductase inhibitor used for the treatment of hyperlipidemia and the prevention of coronary artery disease, significantly lowers plasma cholesterol and low-density lipoprotein cholesterol (LDL-C) levels. It also reduces total plasma triglyceride and apoE concentrations. In view of the direct involvement of apoE in the pathogenesis of atherosclerosis, we have in...

alzheimer’s disease (ad) is the most common cause of dementia caused by complicated interactions between genetic and environmental factors. molecular genetic research has provided valuable information regarding the genetic etiology of the disease. identifying the genetics of ad not only could shed light on disease pathogenesis, but it may also provide potential targets for effective treatment, ...

OBJECTIVE Endothelin (ET)-1 plays a role in vascular reactive oxygen species production and inflammation. ET-1 has been implicated in human atherosclerosis and abdominal aortic aneurysm (AAA) development. ET-1 overexpression exacerbates high-fat diet-induced atherosclerosis in apolipoprotein E(-/-) (Apoe(-/-)) mice. ET-1-induced reactive oxygen species and inflammation may contribute to atheros...

Apolipoprotein E4 (ApoE4), one of three common isoforms of ApoE, is a major risk factor for late-onset Alzheimer disease (AD). ApoE-deficient mice, as well as mice expressing human ApoE4, display impaired learning and memory functions and signs of neurodegeneration. Moreover, ApoE protects against high-fat (HF) diet induced neurodegeneration by its role in the maintenance of the integrity of th...

OBJECTIVE The apolipoprotein E (APOE) ε4 allele is a major genetic risk factor for Alzheimer disease and dementia. However, it remains unclear whether plasma levels of apoE confer additional risk. We tested this hypothesis. METHODS Using 75,708 participants from the general population, we tested whether low plasma levels of apoE at study enrollment were associated with increased risk of futur...

BACKGROUND Several studies have demonstrated a lower apolipoprotein E4 (APOE ε4) allele frequency in African-Americans, but yet an increased age-related prevalence of AD. An algorithm for prevention clinical trials incorporating TOMM40'523 (Translocase of Outer Mitochondria Membrane) and APOE depends on accurate TOMM40'523-APOE haplotypes. METHODS We have compared the APOE and TOMM40'523 phas...

Grafts of autologous keratinocytes genetically altered to secrete a new gene product are a potential vehicle for gene therapy. T o consider the feasibility of such an approach, w e have examined the ability of keratinocytes to secrete and deliver apolipoprotein E (apoE) to the circulation of mice bearing grafts of h u m a n keratinocytes. The grafted keratinocytes secreted two forms of apoE, an...

Despite the important role of apolipoprotein E (apoE) secretion from astrocytes in brain lipid metabolism and the strong association of apoE4, one of the human apoE isoforms, with sporadic and late onset forms of Alzheimer's disease (AD) little is known about the regulation of astrocytic apoE. Utilizing annotated chemical libraries and a phenotypic screening strategy that measured apoE secretio...