OBJECTIVE There is compelling evidence that the plasma apolipoprotein E (APOE) concentration, in addition to the APOE ε2/ε3/ε4 genotype, influences plasma lipoprotein levels, but the functional genetic variants influencing the plasma APOE concentration have not been identified. APPROACH AND RESULTS Genome-wide association studies in 2 cohorts of healthy, middle-aged subjects identified the AP...

The conformations of apolipoproteins on the surfaces of lipoprotein particles affect their physiologic functions. The conformations of apoE on plasma lipoproteins were examined using a panel of eight anti-apoE monoclonal antibodies (MAbs). The antibodies, which reacted with the major isoforms of apoE (E2, E3, and E4), defined at least five epitopes on apoE. Proteolytic fragments and synthetic p...

Apolipoprotein E-deficient (apoE(-/-)) mice have hyperlipidemia and develop spontaneous atherosclerosis in a time-dependent manner. Although macrophage-derived apoE has been shown to prevent the development of atherosclerosis in apoE(-/-) mice, whether it would induce regression of established atherosclerosis is unknown. To determine this, 8-week-old apoE(-/-) mice were transplanted with apoE(+...

Previous studies have demonstrated that macrophage-derived apolipoprotein E (apoE) reduces atherosclerotic lesion formation in lean apoE-deficient ((-/-)) mice. apoE has also been demonstrated to play a role in adipocyte differentiation and lipid accumulation. Because the prevalence of obesity has grown to epidemic proportions, we sought to determine whether macrophage-derived apoE could impact...

etar Alaupovic, an internationally renowned biochemist and lipidologist, died on January 30, 2014, in Oklahoma City at the age of 91 years. Dr Alaupovic was a founder of the modern field of lipoproteins whose ideas continue to have an impact on its development. He performed research and taught at Oklahoma Medical Research Foundation since 1960. In 1964, Dr Alaupovic, known to his colleagues as ...

Large numbers of activated glia are a common pathological feature of many neurodegenerative disorders, including Alzheimer's disease (AD). Several different stimuli, including lipopolysaccharide (LPS), dibutyryl (db)cAMP, and aged amyloid-beta 1-42 (A beta), can induce glial activation in vitro, as measured by morphological changes and the production of pro-inflammatory cytokines and oxidative ...

We have studied synthesis of apolipoprotein E (apo-E) and apo-E mRNA in cultures of peripheral blood human monocyte macrophages (M-M cultures) obtained from a patient with familial apolipoprotein E deficiency. We have found that the M-M cultures of the apo-E-deficient patients contained two apo-E mRNA species with slightly different molecular weight as compared to normal apo-E mRNA. The apo-E m...

apoE deficiency causes hyperlipidemia and premature atherosclerosis. To determine if macrophage-specific expression of apoE would decrease the extent of atherosclerosis, we expressed human apoE in macrophages of apoE-null mice (apoE-/-) and assessed the effect on lipid accumulation in cells of the arterial wall. Macrophage-specific expression of human apoE in normal mice was obtained by use of ...

OBJECTIVES/HYPOTHESIS Age-related hearing loss has a genetic component, but there have been limited genetic studies in this field. Both N-acetyltransferase 2 and apolipoprotein E genes have previously been associated. However, these studies have either used small sample sizes, examined a limited number of polymorphisms, or have produced conflicting results. Here we use a haplotype tagging appro...

BACKGROUND The purpose of this study was to compare apolipoprotein E ε4 (Apo E ε4) and apolipoprotein E ε2 (Apo E ε2) as predictors of cognitive and functional trajectories over 30 months. METHODS This prospective cohort study included 287 community-dwelling memory clinic patients with dementia, mild cognitive impairment, or no cognitive impairment. The Addenbrooke Cognitive Examination, Mini...