Links between genes and risk factors in Alzheimer's disease

Many genes and many environmental risk factors have been implicated in Alzheimer's disease. These are not independent variables and can be linked together. For example the reduction in Alzheimer's disease risk by non-steroidal anti-inflammatories (NSAIDS)can be related to immune and inflammatory genes in Alzheimer's disease, and the reported benefits of statins to cholesterol related genes and the involvenment of Herpes simplex with genes that the virus uses during its life cycle. Carotid and Circle of Willis Atherosclerosis have been linked to Alzheimer's disease and many risk genes are shared between Alzheimer's disease and atherosclerosis.Atherosclerosis or brain hypoperfusion can itself promote amyloid plaque deposition or accelerate that seen in APP transgenic mice . Herpes simplex infection in mice induces entorhinal cortex and hippocampal cell loss and memory deficits as well as beta-amyloid deposition and tau phosphorylation.Chlamydial infections increase atherosclerotic lesions in mice. Alzheimer's disease is multifactorial but the multiple factors are intertwined.It is not just related to beta-amyloid or tau, or even restricted to the CNS. A global approach linking risk and genetic factors is likely to be more relavant to solving the puzzle. Examples of relationships between genes and risk factors are summarised here.