APOE genotype predicts when — not whether — one is predisposed to develop Alzheimer disease

Meyer, M.R.; Tschanz, JoAnn T.; Norton, Maria C.; Welsh‐Bohmer, Kathleen A.; Steffens, David C.; Wyse, Bonita W.; Breitner, John C.S.

doi:10.1038/1206

Cited by 299 publications

(173 citation statements)

References 9 publications

Supporting

Mentioning

160

Contrasting

Unclassified

Order By: Relevance

“…Although this finding has generated fewer biological insights than has the identification, through pedigree studies, of genes implicated in rare, mendelian forms of Alzheimer disease 78 , it has transformed epidemiological and clinical investigation of dementia and related phenotypes. Consequently, it is now known that ApoE4 is associated with the age of onset of Alzheimer disease 95 , the process of cognitive decline in 'normal' aging 96 , altered magnetic resonance imaging findings in asymptomatic individuals 97,98 , risk of chronic traumatic brain injury in boxers 99 and clinical outcome in survivors of traumatic brain injury 100 .…”

Section: Association Studiesmentioning

confidence: 99%

The use of pedigree, sib-pair and association studies of common diseases for genetic mapping and epidemiology

2004

View full text Add to dashboard Cite

Efforts to identify gene variants associated with susceptibility to common diseases use three approaches: pedigree and affected sib-pair linkage studies and association studies of population samples. The different aims of these study designs reflect their derivation from biological versus epidemiological traditions. Similar principles regarding determination of the evidence levels required to consider the results statistically significant apply to both linkage and association studies, however. Such determination requires explicit attention to the prior probability of particular findings, as well as appropriate correction for multiple comparisons. For most common diseases, increasing the sample size in a study is a crucial step in achieving statistically significant genetic mapping results. Recent studies suggest that the technology and statistical methodology will soon be available to make wellpowered studies feasible using any of these approaches.

show abstract

Section: Association Studiesmentioning

confidence: 99%

The use of pedigree, sib-pair and association studies of common diseases for genetic mapping and epidemiology

2004

View full text Add to dashboard Cite

show abstract

“…23 Each allele copy lowers the age of onset by Ϸ10 years. 24 Apolipoprotein E acts as a cholesterol transporter in the brain, with the 4 variant being less efficient in the reuse of membrane lipids and neuronal repair. 25 The 3 and 4 variants play a critical and isoformspecific role in plaque formation.…”

Section: Neurodegeneration and Atherosclerosismentioning

confidence: 99%

Less Atherosclerosis and Lower Blood Pressure for a Meaningful Life Perspective With More Brain

2007

View full text Add to dashboard Cite

T raditional teaching subdivides the dementia syndrome into neurodegenerative Alzheimer's disease (AD), vascular dementia (VaD), and mixed variants. In spite of the vast and continuing literature on the dichotomy between AD and VaD, new emerging concepts highlight the role of cardiovascular risk factors in the pathogenesis of AD, especially in older patients. 1,2 Hypertension is the major player in the pathogenesis of stroke, poststroke dementia, and VaD. AD is the most common cause of dementia, contributing from 45% to Ͼ75% of the cases in Asians and whites, respectively. 3 This review will focus on the role of hypertension as a reversible risk factor in the development of dementia, in particular AD. To set the stage, we will first summarize current insights in the epidemiology of AD, the pathogenesis of VaD and AD, and the association between neurodegeneration and atherosclerosis. Epidemiology of DementiaAcross 36 cross-sectional studies, the prevalence of dementia increased exponentially from 0.3% to 1.0% in subjects aged 60 to 64 years to 10% to 20% in octogenarians and to Ͼ40% in the ninth decade of life. 3 In 15 longitudinal studies, the incidence of dementia showed a similar age-related dependency with rates expressed in new cases per 1000 personyears ranging from 0.4 to 4 at 60 to 64 years to 20 to Ͼ40 at 80 to 85 years. 3 Currently, 24.3 million people have dementia with an annual worldwide incidence of 4.6 million new cases. 4

show abstract

“…Within Caucasians, the ε4 allele frequency in healthy controls is 0.14-0.16, however, this frequency is significantly elevated in AD patients (ranging from 0.36 to 0.42) (14)(15)(16). The inheritance of the ε4 allele increases a person's risk of developing AD in a gene dose-dependent manner and predisposes them to an earlier age of onset (14,17). Conversely, the APOE ε2 allele appears to have a modest protective effect for AD (AlzGene, http://www.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic considerations of the APOE gene

Foraker

2015

Biomolecular Concepts

View full text Add to dashboard Cite

Abstract:The apolipoprotein E (APOE) gene is robustly linked with numerous physiological conditions, including healthy aging, altered cardiovascular fitness, and cognitive function. These connections have been established primarily by phenotype-genotype association studies using APOE's three common genetic variants (ε2, ε3, and ε4). These variants encode for the three apoE protein isoforms (E2, E3, and E4), which have slightly different structures and, consequently, distinct functions in lipid metabolism. However, the differential lipid binding and transferring properties of these isoforms cannot fully explain the association of APOE with such a wide range of physiological phenotypes. One potential explanation for APOE's pleiotropic roles may lie in its unique epigenetic properties. In this article, we present a brief review of the APOE gene and protein, its disease associations, and epigenetic components, with a focus on DNA methylation. We close with a discussion of the prospective epigenetic implications of APOE in disease.

show abstract

APOE genotype predicts when — not whether — one is predisposed to develop Alzheimer disease

Cited by 299 publications

References 9 publications

The use of pedigree, sib-pair and association studies of common diseases for genetic mapping and epidemiology

The use of pedigree, sib-pair and association studies of common diseases for genetic mapping and epidemiology

Less Atherosclerosis and Lower Blood Pressure for a Meaningful Life Perspective With More Brain

Epigenetic considerations of the APOE gene

Contact Info

Product

Resources

About