Epidemiology and Etiology of Alzheimer’s disease: From Genetic to Non- Genetic Factors

Abstract

At present, the etiology of Alzheimer's disease (AD) is still unclear, but both genetic and non-genetic factors are thought to take part in the etiopathogenesis of AD. Epidemiologic researches revealed that genetic factors played a decisive role in the development of both early-onset AD (EOAD) and late-onset AD (LOAD). The mutations in APP, PSEN1 and PSEN2 are inherited in a Mendelian fashion and directly lead to the EOAD, while recent genome-wide association studies have identified numbers of risky genes, which influences the susceptibility to LOAD. Although genetic factors are inherited and fixed, non-genetic factors, such as occupational exposures (exposure to pesticides, electromagnetic fields, organic solvents and volatile anesthetics), pre-existing medical conditions (cerebrovascular disease, hypertension, diabetes, dyslipidemia, traumatic brain injury, depression and cancer) and lifestyle factors (smoking, consumptions of alcohol and coffee, body mass index, physical activity and cognitive activity), are partly environmentally-determined. Timely interventions targeted at these non-genetic risk factors may offer opportunities for prevention and treatment of AD. In the future, more high-quality and large-sample epidemiologic studies are needed to identify risk factors for AD, and the interaction models between genetic and non-genetic risk factors required further investigation. In addition, public health campaigns targeted at modification of non-genetic risk factors should be developed among population at high risk of AD.

Characterization of AD-like phenotype in aged APPSwe/PS1dE9 mice

“…The pathogenesis of AD remains unclear and may likely be attributed to the combined effects of numerous factors, such as hereditary, environment, lifestyle, metabolic disturbance, and brain trauma (Querfurth and Laferla 2010;Jiang et al 2013). However, aging is a significant risk factor for the onset of AD (Ballard et al 2011;Bernick et al 2012;Langbaum et al 2013).…”

TYROBP in Alzheimer’s Disease

“…As the most common neurodegenerative disorder in humans, Alzheimer's disease (AD) is characterized by the formation of extracellular amyloid plaques containing aggregated amyloid-β (Aβ) peptides, which is believed to play an important role in the pathogenesis of this disease [1,2]. Accumulating pieces of evidence have indicated that microglia activation induced by Aβ is a "double-edged sword" event in AD.…”

The Role of PICALM in Alzheimer’s Disease

“…AD has been classified into two major forms: the early-onset type (<65 years of age) and late-onset type (LOAD; >65 years of age). Its etiology and trajectory can be characterized as a complex interaction effect between environmental and genetic factors [1][2][3][4]. For the genetic realm specifically, mutations in multiple loci have been associated with risk of developing AD of two forms.…”