Early-onset Alzheimer's disease in Scotland: environmental and familial factors

Abstract

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.

Lifetime principal occupation and risk of Alzheimer's disease in the Kungsholmen project

“…First, subjects in the category of manual work involving goods production in our population included workers such as tailors and dressmakers, house constructers and related workers, furniture makers and carpenters, mechanical technicians, formers, typographers, welders, and metal workers. These individuals, especially those that were involved in goods production, could be exposed to multi-toxics in the work environment [Cohen, 1994;Whalley, 2001]. Studies have suggested that exposure to neurotoxic materials (e.g., heavy metals, solvents, pesticides, or defoliants) and electromagnetic fields may lead to global lesions of several neurological diseases, including Alzheimer's disease and other dementias [Kukull et al, 1995;Sobel et al, 1996;Hébert et al, 2000;Tyas et al, 2001].…”

Paternal age effect on age of onset in bipolar I disorder is mediated by sex and family history

“…We could not control for interactions between advanced paternal age and environmental factors that might have influenced the BPI onset in probands. Interaction between older paternal age and exposure of the fathers to toxic chemicals having influence on the disease AO in men was described by Whalley [2001] in Alzheimer's disease in offspring of Scottish coal miners. Similarly, exposure of the probands to long‐lasting psychosocial stressors may trigger an earlier AO through depressive episodes.…”

“…In Alzheimer's disease, the research has focussed on the relationship between the age‐of‐onset (AO) of the disorder and the parental age at the child's birth. A Scottish study [Whalley, 2001] found a sex‐specific effect consisting of a negative correlation between paternal age and AO of the disease only in men. There was no correlation between paternal age and Alzheimer's AO in women.…”

Modifier variant of METTL13 suppresses human GAB1–associated profound deafness

“…A modifier variant can enhance or suppress the phenotype of a monogenic disorder as well as alter the onset, severity, or progression of the phenotype (1)(2)(3)(4)(5). The site of action of modifiers can be at any point from transcription to posttranslational modification of the target genes.…”