Challenges of Exploratory Visualization of Gene-environment Interaction in Alzheimer's Disease

BackgroundAlzheimer's disease (AD) is a common, complex, age-related disorder in which both genetic and environmental factors are important.AimsTo integrate recent studies on genetic and environmental factors in AD into a multi-factorial disease model.MethodDisease models to explain gene-environment interaction in cardiovascular disease are related to observations on AD.ResultsInformative, community-based studies on the genetic epidemiology of AD are rare. Putative risk factors from the Scottish studies include increased paternal age in AD men and coal mining as paternal occupation in both AD and vascular dementia. Migration effects suggest that environmental factors in high-incidence AD areas are important during adult life.ConclusionsThe studies summarised do not provide sufficient data to support a single comprehensive disease model of gene-environment interaction in AD. Future studies will require very large (≥600) sample sizes, molecular genetic analysis, and environmental data that span neurodevelopment and the period between disease onset and appearance of clinical symptoms.

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Gene-Environment Interaction Research and Transgenic Mouse Models of Alzheimer's Disease (Erratum)

International Journal of Alzheimer s Disease ◽

10.4061/2010/356862 ◽

2010 ◽

Vol 2010 ◽

pp. 1-1 ◽

Cited By ~ 1

Author(s):

L. Chouliaras ◽

A. S. R. Sierksma ◽

G. Kenis ◽

J. Prickaerts ◽

M. A. M. Lemmens ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Transgenic Mouse ◽

Mouse Models ◽

Environment Interaction ◽

Transgenic Mouse Models ◽

Gene Environment Interaction ◽

Gene Environment ◽

Interaction Research

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Gene–Environment Interaction in Alzheimer’s Disease

American Journal of Alzheimer s Disease & Other Dementias® ◽

10.1177/1533317512456067 ◽

2012 ◽

Vol 27 (7) ◽

pp. 496-503 ◽

Cited By ~ 10

Author(s):

Neeraj Kumar Singh ◽

Neelam Chhillar ◽

B. D. Banerjee ◽

Kiran Bala ◽

Ajit Kumar Mukherjee ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Environment Interaction ◽

Gene Environment Interaction ◽

Gene Environment

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Apolipoprotein E epsilon 4 genotype and a physically active lifestyle in late life: analysis of gene–environment interaction for the risk of dementia and Alzheimer's disease dementia

Psychological Medicine ◽

10.1017/s0033291713001918 ◽

2013 ◽

Vol 44 (6) ◽

pp. 1319-1329 ◽

Cited By ~ 40

Author(s):

T. Luck ◽

S. G. Riedel-Heller ◽

M. Luppa ◽

B. Wiese ◽

M. Köhler ◽

...

Keyword(s):

Physical Activity ◽

Alzheimer’S Disease ◽

Apolipoprotein E ◽

Late Life ◽

Environment Interaction ◽

Additive Interaction ◽

Free Survival ◽

Gene Environment Interaction ◽

Gene Environment

BackgroundAs physical activity may modify the effect of the apolipoprotein E (APOE) ε4 allele on the risk of dementia and Alzheimer's disease (AD) dementia, we tested for such a gene–environment interaction in a sample of general practice patients aged ⩾75 years.MethodData were derived from follow-up waves I–IV of the longitudinal German study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe). The Kaplan–Meier survival method was used to estimate dementia- and AD-free survival times. Multivariable Cox regression was used to assess individual associations of APOE ε4 and physical activity with risk for dementia and AD, controlling for covariates. We tested for gene–environment interaction by calculating three indices of additive interaction.ResultsAmong the randomly selected sample of 6619 patients, 3327 (50.3%) individuals participated in the study at baseline and 2810 (42.5%) at follow-up I. Of the 2492 patients without dementia included at follow-up I, 278 developed dementia (184 AD) over the subsequent follow-up interval of 4.5 years. The presence of the APOE ε4 allele significantly increased and higher physical activity significantly decreased risk for dementia and AD. The co-presence of APOE ε4 with low physical activity was associated with higher risk for dementia and AD and shorter dementia- and AD-free survival time than the presence of APOE ε4 or low physical activity alone. Indices of interaction indicated no significant interaction between low physical activity and the APOE ε4 allele for general dementia risk, but a possible additive interaction for AD risk.ConclusionsPhysical activity even in late life may be effective in reducing conversion to dementia and AD or in delaying the onset of clinical manifestations. APOE ε4 carriers may particularly benefit from increasing physical activity with regard to their risk for AD.

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Gene-Environment Interaction Research and Transgenic Mouse Models of Alzheimer's Disease

International Journal of Alzheimer s Disease ◽

10.4061/2010/859101 ◽

2010 ◽

Vol 2010 ◽

pp. 1-27 ◽

Cited By ~ 4

Author(s):

L. Chouliaras ◽

A. S. R. Sierksma ◽

G. Kenis ◽

J. Prickaerts ◽

M. A. M. Lemmens ◽

...

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Environmental Factors ◽

Genetic Manipulation ◽

Transgenic Animal ◽

Environment Interaction ◽

Gene Environment ◽

Transgenic Animal Models ◽

Mediating Mechanisms

The etiology of the sporadic form of Alzheimer's disease (AD) remains largely unknown. Recent evidence has suggested that gene-environment interactions (GxE) may play a crucial role in its development and progression. Whereas various susceptibility loci have been identified, like the apolipoprotein E4 allele, these cannot fully explain the increasing prevalence of AD observed with aging. In addition to such genetic risk factors, various environmental factors have been proposed to alter the risk of developing AD as well as to affect the rate of cognitive decline in AD patients. Nevertheless, aside from the independent effects of genetic and environmental risk factors, their synergistic participation in increasing the risk of developing AD has been sparsely investigated, even though evidence points towards such a direction. Advances in the genetic manipulation of mice, modeling various aspects of the AD pathology, have provided an excellent tool to dissect the effects of genes, environment, and their interactions. In this paper we present several environmental factors implicated in the etiology of AD that have been tested in transgenic animal models of the disease. The focus lies on the concept of GxE and its importance in a multifactorial disease like AD. Additionally, possible mediating mechanisms and future challenges are discussed.

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