Here, we review the effects and implications of the putative transcriptional role of ApoE4 and propose a model of Alzheimer's disease that focuses on the transcriptional nature of ApoE4 and its downstream effects, with the aim that this knowledge will help to define the role ApoE4 plays as a risk factor for AD, aging, and other processes such as inflammation and cardiovascular disease.
To evaluate the utility of this strategy in identifying new biological pathways relevant to cardiovascular disease pathophysiology, we performed studies in a cell-model system to experimentally validate the functional significance of an especially novel genetic association with circulating apolipoprotein E levels.
Besides its well-established role in pathology of CVD, it is also implicated in neurodegenerative diseases and recent new data on adipose-produced apoE point to a novel metabolic role for apoE in obesity.
These improvements were subsequent to the disclosure of genetic information and occurred mainly in the APOE ε4-positive members of the former control group, that is, those who were at increased genetic risk for CVD but had not been informed of their status before the end of the intervention.
Conclusions- These exploratory results suggest that APOE-ε4 carriers may be more susceptible to the beneficial or adverse impact of fatty acids on cardiovascular disease and mortality.
Apolipoprotein E gene polymorphism modifies fasting total cholesterol concentrations in response to replacement of dietary saturated with monounsaturated fatty acids in adults at moderate cardiovascular disease risk.
A multiple reaction monitoring (MRM) assay was developed for precise quantitation of 87 plasma proteins including the three isoforms of apolipoprotein E (APOE) associated with cardiovascular diseases using nanoscale liquid chromatography separation and stable isotope dilution strategy.
The apolipoprotein E (APOE) risk allele (ɛ4) is associated with higher total cholesterol (TC), amplified response to saturated fatty acid (SFA) reduction, and increased cardiovascular disease.
The APOE*4 allele is a risk factor for cardiovascular disease and could contribute to the development of the metabolic syndrome (MetS) as it may affect all MetS components.
Genetic polymorphisms of apolipoprotein E (APOE) are associated with various health conditions and diseases, such as Alzheimer's disease, cardiovascular diseases, type 2 diabetes, etc.
The association of APOE e4 with cognitive function was strongly amplified in the presence of hypercholesterolemia and cardiovascular disease in both independent cohorts; hypercholesterolemia was associated with cognitive function only among APOE e4 carriers in the presence of cardiovascular disease.
A structural equation model using age, education, race, and apolipoprotein E (APOE) genotype (number of ɛ2 and ɛ4 alleles) as predictors and latent AD pathology and cerebrovascular disease (CVD) pathology as mediators fit the data well (RMSEA = 0.031; CFI = 0.957).
People with allelic variation in four genes related to cardiovascular diseases and metabolism were more likely to die: apolipoprotein (APO)C1 GG and AG carriers, APOE ɛ4 carriers, insulin-degrading enzyme (IDE) TC carriers, and phosphatidylinositol 3-kinase (PI3KCB) GG carriers.