Risk and protective factors for sporadic Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of senile dementia. There are 24.3 million people suffering from this progressive neurodegenerative disorder worldwide. A century ago, AD was characterized with regard to the clinical manifestations and pathology for the first time. Up till now, there is a lack of full understanding of the underlying causes and molecular mechanisms leading to this progressive form of dementia. The majority of AD cases occur sporadically, what suggested that they could arise through interactions among various genetic and environmental factors. Current epidemiological investigations show that midlife hypertension, cardiovascular diseases, hypercholesterolemia, diabetes, obesity, inflammation, and viral infections can significantly contribute to the development and progression of AD, whereas active engagement in social, mental and physical activities may delay the onset of the disease. Apolipoprotein E (ApoE) is considered as the main genetic risk factor in the sporadic AD that is closely connected to lipid metabolism. Other genes involved in the disease pathways related to AD pathology in addition to cholesterol metabolism, neuroinflammation, amyloid and tau cascade, neuronal signalling, and plasticity are under investigation. In spite of the significant progress achieved, it is still not clear how genetic vulnerability and environmental exposures may contribute to the susceptibility of the disease. Therefore, understanding the role of disease-related risk factors for AD pathogenesis may help to identify specific modifiable risk factors that could provide possibility for the prevention of Alzheimer's dementia.