Dataset Information

APOE and Alzheimer's Disease: From Lipid Transport to Physiopathology and Therapeutics.

ABSTRACT: Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by extracellular amyloid ? (A?) and intraneuronal tau protein aggregations. One risk factor for developing AD is the APOE gene coding for the apolipoprotein E protein (apoE). Humans have three versions of APOE gene: ?2, ?3, and ?4 allele. Carrying the ?4 allele is an AD risk factor while carrying the ?2 allele is protective. ApoE is a component of lipoprotein particles in the plasma at the periphery, as well as in the cerebrospinal fluid (CSF) and in the interstitial fluid (ISF) of brain parenchyma in the central nervous system (CNS). ApoE is a major lipid transporter that plays a pivotal role in the development, maintenance, and repair of the CNS, and that regulates multiple important signaling pathways. This review will focus on the critical role of apoE in AD pathogenesis and some of the currently apoE-based therapeutics developed in the treatment of AD.

SUBMITTER: Husain MA

PROVIDER: S-EPMC7925634 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

APOE and Alzheimer's Disease: From Lipid Transport to Physiopathology and Therapeutics.

Husain Mohammed Amir MA Laurent Benoit B Plourde Mélanie M

Frontiers in neuroscience 20210217

Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by extracellular amyloid β (Aβ) and intraneuronal tau protein aggregations. One risk factor for developing AD is the <i>APOE</i> gene coding for the apolipoprotein E protein (apoE). Humans have three versions of <i>APOE</i> gene: ε2, ε3, and ε4 allele. Carrying the ε4 allele is an AD risk factor while carrying the ε2 allele is protective. ApoE is a component of lipoprotein particles in the plasma at the periphery, ...[more]

PMID: 33679311

Similar Datasets

Project description:The apolipoprotein E (APOE) and tau proteins play important roles in the pathological development of Alzheimer's disease (AD). Many studies have shown an association between the APOE gene and AD. Association between AD and the newly discovered saitohin (STH) gene, nested within the intron of the tau gene, has been reported. The present study aimed to elucidate the association between APOE and AD, and between STH and AD in our sample.The functional polymorphisms, rs429358 and rs7412, in the APOE gene (which together define the epsilon2, epsilon3, and epsilon4 alleles), and the Q7R SNP in the STH gene, were genotyped in 369 patients with AD and 289 healthy European-Americans. The associations between these two genes and AD were analyzed in a case-control design.Consistent with previously reported results, the frequencies of the APOE epsilon4 allele, epsilon4/epsilon4 genotype and epsilon3/epsilon4 genotype were significantly higher in AD cases than controls; the epsilon4/epsilon4 genotype frequency was significantly higher in early-onset AD (EOAD) than late-onset AD (LOAD); the frequencies of the epsilon2 allele, epsilon3 allele, epsilon3/epsilon3 genotype and epsilon2/epsilon3 genotype were significantly lower in AD cases than controls. Positive likelihood ratios (LRs+) of APOE alleles and genotypes increased in a linear trend with the number of epsilon4 alleles and decreased in a linear trend with the number of epsilon2 or epsilon3 alleles. There was no significant difference in the STH allele and genotype frequency distributions between AD cases and controls.This study confirmed that the epsilon4 allele is a dose-response risk factor for AD and the epsilon4/epsilon4 genotype was associated with a significantly earlier age of onset. Moreover, we found that the epsilon2 allele was a dose-response protective factor for AD and the epsilon3 allele exerted a weaker dose-response protective effect for risk of AD compared with epsilon2. In a clinical setting, APOE genotyping could offer additional biological evidence of whether a subject may develop AD, but it is not robust enough to serve as an independent screening or predictive test in the diagnosis of AD. STH variation was not significantly associated with AD in our sample.

Dataset Information

APOE and Alzheimer's Disease: From Lipid Transport to Physiopathology and Therapeutics.

Publications

APOE and Alzheimer's Disease: From Lipid Transport to Physiopathology and Therapeutics.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets