Alzheimer Disease/genetics* ; Animals ; Apolipoprotein E4/metabolism* ; Gene-Environment Interaction ; Hippocampus/metabolism* ; Male ; Noise/adverse effects* ; Rats

Apolipoprotein E is a plasma protein that has an important role in transport and metabolism of lipids in serum as well as central nervous system. Among the 3 common alleles, the ε2 allele has the most stable structure followed by ε3 and ε4 in order. There is evidence for a deleterious role of ε4 allele by atherosclerosis and amyloid beta accumulation in brain and body. The presence and gene dose of ε4 allele are risk factors for late-onset Alzheimer's disease. Apolipoprotein E ε4 may have a role in the pathology of amyloid beta and tau and it has a strong relationship with the early onset of late-onset Alzheimer's disease. However, early-onset Alzheimer's disease has a weaker relationship with ε4 allele of apolipoprotein E.
Alleles ; Alzheimer Disease ; Amyloid ; Apolipoprotein E4* ; Apolipoproteins* ; Atherosclerosis ; Brain ; Central Nervous System ; Cognitive Aging* ; Metabolism ; Pathology ; Plasma ; Risk Factors*

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease featuring progressive cognitive impairment. Although the etiology of late-onset AD remains unclear, the close association of AD with apolipoprotein E (APOE), a gene that mainly regulates lipid metabolism, has been firmly established and may shed light on the exploration of AD pathogenesis and therapy. However, various confounding factors interfere with the APOE-related AD risk, raising questions about our comprehension of the clinical findings concerning APOE. In this review, we summarize the most debated factors interacting with the APOE genotype and AD pathogenesis, depict the extent to which these factors relate to APOE-dependent AD risk, and discuss the possible underlying mechanisms.
Alzheimer Disease/pathology* ; Apolipoprotein E4/genetics* ; Apolipoproteins E/genetics* ; Genotype ; Humans ; Lipid Metabolism ; Neurodegenerative Diseases ; Risk Factors

BACKGROUND: Apo E lipoprotein is polymorphic and exists in three common isoforms (E2, E3 and E4), which are the gene products of three apo E alleles, e2, e3 and e4. Apo E lipoprotein plays an important role in the regulation of the lipid metabolism through its ability to bind to receptors. Depending on the genotypes apo E polymorphism is either protective or increases risk for atherosclerosis and coronary artery disease. The purpose of this study is to evaluate 1) the association between apo E allele and the development of coronary artery disease, 2) the association between apo E alleles and dyslipidemia in Korean males. METHODS: We studied 241 patients with angiographically verified coronary artery disease and 257 male subjects without evidence of coronary artery disease. Apo E genotyping was determined with the INNO-LiPA Apo E kit (Innogenetics, Belgium), which is based on reverse hybridization. RESULTS: There was a higher frequency of the apo e4 allele in subjects with coronary artery disease than in normal controls. The frequencies of apo E genotype were not significantly associated with apo e2 were associated with higher levels of triglyceride and lower LDL, and the subjects with apo e4 had lower levels of HDL cholesterol. CONCLUSION: ApoE polymorphism is a genetic marker for risk of the development of coronary artery disease and an important determinant of dyslipidemia.
Alleles ; Apolipoprotein E2 ; Apolipoprotein E4 ; Apolipoproteins E ; Apolipoproteins* ; Atherosclerosis ; Cholesterol, HDL ; Coronary Artery Disease* ; Coronary Vessels* ; Dyslipidemias ; Genetic Markers ; Genotype ; Humans ; Lipid Metabolism ; Lipoproteins ; Male* ; Protein Isoforms ; Triglycerides

PURPOSE: Apolipoprotein E (Apo E) plays a major role in lipoprotein metabolism and lipid transport. Many investigators have described that Apo E polymorphisms is one of the most important genetic determinants for cardiovascular disease. The purpose of this study was to evaluate the association between Apo E polymorphisms and serum lipid profiles in obese adolescent. METHODS: We measured the serum concentrations of glucose, apolipoprotein (Apo) A1, Apo B, total cholesterol (TC), triglyceride (TG), HDL and LDL-cholesterol after overnight fasting in obese adolescent. Apo E polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: 86 obese adolescents participated in this study. The body mass index (BMI) of participants were excess of 95 percentile by age and sex. Male to female ratio was 1.7 and mean age of study group was 16.2+/-1.8 years. Mean BMI was 27.4+/-2.5 kg/m2. The frequency of epsilon2, epsilon3 and epsilon4 allele were 8.1%, 87.2% and 4.7% respectively. Study populations were classified into the following three genotypes 1) Apo E2 group (n=13, 15.1%) carrying either the epsilon2/epsilon2 or epsilon2/epsilon3 2) Apo E3 group (n=65, 75.6%) carrying the most frequent epsilon3/epsilon3 3) Apo E4 group (n=8, 9.3%) carrying either the epsilon3/epsilon4 or epsilon4/epsilon4. No differences were found among Apo E genotypes concerning age, sex, weight, height and BMI. Apo B and LDL-cholesterol concentrations were significantly higher in the Apo E4 group (P<0.05). No association were found between Apo E genotypes and glucose, Apo A1, TC, TG and HDL. CONCLUSIONS: We confirmed that serum concentrations Apo B and LDL-cholesterol were influenced by Apo E genotypes. Apo E polymorphisms seems to influence some alteration of lipid metabolism associated with obesity in adolescent.
Adolescent ; Alleles ; Apolipoprotein A-I ; Apolipoprotein E2 ; Apolipoprotein E3 ; Apolipoprotein E4 ; Apolipoproteins ; Apolipoproteins B ; Apolipoproteins E ; Body Mass Index ; Cardiovascular Diseases ; Cholesterol ; Fasting ; Female ; Genotype ; Glucose ; Humans ; Lifting ; Lipid Metabolism ; Lipoproteins ; Male ; Obesity ; Research Personnel

PURPOSE: Weight changes, especially weight gain, is a side effect of antiepileptics(especially valproate and carbamazepine). This may be sufficiently severe to cause noncompliance or to require the withdrawal of effective treatment. Unfortunately, the exact mechanism of weight change is not illustrated. Several reports and our experiment suggested that weight gain highly correlated with a familial tendency of obesity. The genetic makeup is a possible factor among those of the factors that influence the impact of obesity on lipid metabolism. The purpose of this prospective, random trial clinical study was to evaluate the coherence between the changes of weight and lipid profiles and apolipoprotein E polymorphism in children with antiepileptics. METHODS: We studied 60 epileptic children treated with antiepileptics. We measured the body mass index and lipid profiles:total cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol. Changes of appetite and family histories of obesity were examined. The apolipoprotein E gene polymorphisms of the patients were analyzed by the amplification refractory mutation system method. RESULTS: The body mass indexes of patient were significantly increased in all patient groups. The epileptic children who had E4 genotype showed higher frequencies of hypertriglyceridemia, hypercholesterolemia, and decreased level of HDL-cholesterol than other types. There was no significant difference between Apo E subtype with family histories of obesity and body mass index. CONCLUSION: An association with Apo E4 genotype and changes of serum lipid were demonstrated significantly in children on antiepileptics. But there was no significant difference between Apo E subtype and body mass index.
Anticonvulsants* ; Apolipoprotein E4 ; Apolipoproteins E ; Apolipoproteins* ; Appetite ; Body Mass Index ; Body Weight* ; Child* ; Cholesterol ; Genotype ; Humans ; Hypercholesterolemia ; Hypertriglyceridemia ; Lipid Metabolism ; Obesity ; Prospective Studies ; Triglycerides ; Valproic Acid ; Weight Gain

OBJECTIVETo explore the relations among apolipoprotein E4, Tau protein and glycogen synthase kinase 3β (GSK-3β).

METHODSU87 cells were transfected with pIRES-EGFP (control) or the recombinant plasmids ApoE4/pIRES-EGFP or ApoE3/pIRES-EGFP, and the expression levels of p-Tau/Tau and GSK-3β in the cells were examined with Western blotting. To further confirm the effect of ApoE on GSK-3β and p-Tau expressions, a short interfering RNA (siRNA) targeting ApoE (ApoE-siRNA) was transfected into U87 cells via Lipofectamine 2000 and the protein expressions were examined 24 h later.

RESULTSCompared with those in the control group, the expressions levels of both GSK-3β and p-Tau/Tau increased significantly in the cells transfected with ApoE4 and ApoE3 plasmids (P<0.01), and the ApoE4 plasmid produced a more potent effect than the ApoE3 plasmid on the protein expressions (P<0.01). ApoE knockdown resulted in significantly reduced expressions of GSK-3β (P<0.001) and p-Tau (P<0.01) in the cells.

CONCLUSIONApoE4 can enhance Tau phosphorylation though upregulating GSK-3β, which sheds light on a new role of ApoE4 in Alzheimer's disease.

Alzheimer Disease ; genetics ; Apolipoprotein E3 ; genetics ; Apolipoprotein E4 ; genetics ; Cell Line ; Gene Silencing ; Glycogen Synthase Kinase 3 beta ; genetics ; metabolism ; Humans ; Phosphorylation ; RNA, Small Interfering ; genetics ; Transfection ; tau Proteins ; metabolism

Alzheimer's disease (AD) is an increasing epidemic threatening public health. Both men and women are susceptible to the disease although women are at a slightly higher risk. The prevalence of AD rises exponentially in elderly people from 1% at age of 65 to approximately 40%-50% by the age of 95. While the cause of the disease has not been fully understood, genetics plays a role in the onset of the disease. Mutations in three genes (APP, PSEN1, and PSEN2) have been found to cause AD and APOE4 allele increases the risk of the disease. As human genomic research progresses, more genes have been identified and linked with AD. Genetic screening tests for persons at high risk of AD are currently available and may help them as well as their families better prepare for a later life with AD.
Aged ; Aged, 80 and over ; Aging ; genetics ; metabolism ; Alzheimer Disease ; diagnosis ; epidemiology ; genetics ; Amyloid beta-Protein Precursor ; genetics ; metabolism ; Apolipoprotein E4 ; genetics ; Genetic Predisposition to Disease ; genetics ; Genetic Testing ; trends ; Humans ; Mutation ; genetics ; Presenilins ; genetics ; metabolism ; Risk Factors

Specific apolipoprotein (apo) E genotype has been suggested as a risk factor for atherosclerosis in the general population. Lipid metabolism is known to be modulated by apo E genotype. In this study, we measured apo E genotype, lipoprotein (a)[Lp (a)], apo A phenotype and other lipoproteins in 50 CAPD patients, and evaluated the association of lipid parameters with atherosclerotic cardiovascular disease. Dipyridamole thallium scan with SPECT and ankle- arm blood pressure index (AABI) were performed in all the subjects. The patients who had positive finding in at least one of the two test were considered to have atherosclerotic cardiovascular disease [CVD (+)]. Fifteen patients had evidence of cardiovascular disease. Serum Lp (a) concentration (median; interquartile range) of CVD (+) patients (n=15, 62.0 mg/dl; 29.5-82.3) was not different from that of CVD (-) patients (n=35, 65.1mg/dl; 34.3-89.9). The frequency distribution of apo (a) phenotype of CVD (+) patients did not differ from that of CVD (-) patients. In addition, there were no differences of other lipoproteins levels and lipid profiles between two group. However, significant difference in the frequency distribution of apo E genotype (E2; 6.7 vs 20%, E3; 40 vs 68.6%, E4; 53.3 vs between CVD (+) and CVD (-) patients. After stratifying the subjects according to the apo E genotype, we observed no difference of lipid profiles, apolipoproteins and Lp (a) concentration in E2, E3, E4. Multivariate regression analysis of risk factors for CVD revealed age and the presence of apo E4 phenotype as independent risk factors of atherosclerotic cardiovascular disease. In conclusion, Apo E4 genotype could be an independent risk factor of atherosclerotic cardiovascular disease in CAPD patients.
Apolipoprotein E4 ; Apolipoproteins E ; Apolipoproteins* ; Arm ; Atherosclerosis ; Blood Pressure ; Cardiovascular Diseases* ; Dipyridamole ; Genotype ; Humans ; Lipid Metabolism ; Lipoproteins ; Peritoneal Dialysis, Continuous Ambulatory* ; Phenotype ; Risk Factors ; Thallium ; Tomography, Emission-Computed, Single-Photon

This study aimed to investigate the independent and interactive influences of apolipoprotein E (APOE) epsilon4 and beta-amyloid (Abeta) on multiple cognitive domains in a large group of cognitively normal (CN) individuals and patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Participants were included if clinical and cognitive assessments, amyloid imaging, and APOE genotype were all available from the Alzheimer's Disease Neuroimaging Initiative database (CN = 324, MCI = 502, AD = 182). Individuals with one or two copies of epsilon4 were designated as APOE epsilon4 carriers (epsilon4+); individuals with no epsilon4 were designated as APOE epsilon4 non-carriers (epsilon4-). Based on mean florbetapir standard uptake value ratios, participants were classified as Abeta burden-positive (Abeta+) or Abeta burden-negative (Abeta-). In MCI, APOE epsilon4 effects were predominantly observed on frontal executive function, with epsilon4+ participants exhibiting poorer performances; Abeta positivity had no influence on this effect. Abeta effects were observed on global cognition, memory, and visuospatial ability, with Abeta+ participants exhibiting poorer performances. Measures of frontal executive function were not influenced by Abeta. Interactive effects of APOE epsilon4+ and Abeta were observed on global cognition and verbal recognition memory. Abeta, not APOE epsilon4+, influenced clinical severity and functional status. The influences of APOE epsilon4+ and Abeta on cognitive function were minimal in CN and AD. In conclusion, we provide further evidence of both independent and interactive influences of APOE epsilon4+ and Abeta on cognitive function in MCI, with APOE epsilon4+ and Abeta showing dissociable effects on executive and non-executive functions, respectively.
Aged ; Aged, 80 and over ; Alzheimer Disease/genetics/pathology ; Amyloid beta-Peptides/*metabolism ; Aniline Compounds/chemistry ; Apolipoprotein E4/*genetics ; Brain/radiography ; Cognition ; Databases, Factual ; Demography ; Ethylene Glycols/chemistry ; Female ; Genotype ; Humans ; Male ; Mild Cognitive Impairment/genetics/*pathology ; Positron-Emission Tomography