The role of apolipoprotein E in neurodegeneration and cardiovascular disease

Abstract

Apolipoprotein E (ApoE) is an abundant plasma protein that interacts with low density lipoprotein receptors and other proteins, participating in the transport of cholesterol and lipids. Research has revealed many other roles for this multifunctional protein. ApoE is polymorphic and exists in three major isoforms: ApoE2, ApoE3 (the most common isoform) and ApoE4, which differ by only one amino acid, at positions 112 and 158. The altered binding to lipids and receptors by ApoE isoforms E2 and E4 results in an elevated risk for neurological, cerebrovascular and cardiovascular pathologies. Most notably, ApoE4 is associated with an elevated risk (relative to E3) for Alzheimer's disease. The application of mass spectrometry for genotyping and also direct measurement of ApoE protein isoforms is a recent development and is well suited to high-throughput applications. The precise quantification of protein isoforms will allow better characterization of effects resulting from heterozygous APOE genotypes.

Defining the Relationship Between Hypertension, Cognitive Decline, and Dementia: a Review

“…Alzheimer’s disease, cerebrovascular disease, and cardiovascular disease have shared genetic contributions [76,77], and approximately 50% of individuals diagnosed with Alzheimer’s disease display significant cerebrovascular pathology on autopsy [78,79]. Together, these findings suggest that cardiovascular disease, Alzheimer’s disease, and vascular dementia may have an overlapping pathophysiology [80–82].…”

Insulin resistance and cognitive dysfunction

“…ApoE is a polymorphic protein with common variants known as E2, E3, and E4 that are encoded by the ε2, ε3, and ε4 alleles, respectively, with population frequencies of approximately 8, 77 and 15%, respectively [97][98][99]. ApoE4 has been confirmed as an important factor for dementia and progress of cognitive impairment in the elderly [100,101].…”

Associations between <b><i>Apolipoprotein E</i></b> Gene Polymorphisms and Cardiovascular Complications of Uremic Patients on Maintenance Hemodialysis

“…Evidence was provided by a previous study that elevated plasma lipid was the main risk for cardiovascular disease and ApoE polymorphisms influence the lipid composition in plasma and the progression of cardiovascular disease through other biochemical pathway [11]. Zhang et al [35] observed that ε4 allele exerted a high risk on Chinese coronary heart disease patients.…”

“…And cardiovascular complications have been demonstrated as a main cause of morbidity and mortality in patients with kidney failure [10]. Interestingly, it has been reported that apolipoprotein E (ApoE) is a genetic risk factor for some cardiovascular diseases, such as myocardial infarction and coronary artery disease [11].…”