What do we know about risk factors for Alzheimer's disease? We know that family history is a risk factor. The strongest association is seen in individuals who have a first-degree relative—a mother, father, sister, or brother—with the disease, such that they have a two- to three-fold increase risk to develop the disease compared to the general population risk. The general population risk is about 10 to 15 percent, and therefore a person with a first-degree relative would have about a 20- to 30-percent risk of getting AD in their lifetime.
That risk probably increases with the number of affected individuals in the family, but there is no good study to quantify the risk unless it you can see a Mendelian pattern of inheritance, such as an autosomal-dominant pattern of inheritance. However, we usually only see those patterns of inheritance in early-onset familial Alzheimer's disease.
We know of four genes associated with Alzheimer's disease, and you have probably heard of those genes. The APOE gene is associated with late-onset disease. The amyloid precursor protein (APP), presenilin-1 (PS1) and presenilin-2 (PS2) are associated with early-onset familial Alzheimer's disease.
There are always new studies in the literature or on the news. Genetics and Alzheimer's disease seems to be a popular topic. Linkage studies have consistently shown findings on chromosomes 9, 10, and 12, and there are some candidate genes that are being considered. I will explain at the end of my talk some of the linkage studies that we are doing at Columbia.
We think that Alzheimer's disease is a complex disease and that it is not purely genetic, not purely environmental. It is probably multiple genes interacting along with environmental factors. I would like to mention some of these other factors. Age, of course, is a risk factor for the disease; gender and ethnicity; some studies have shown head trauma is a risk factor for disease; and years of education. I am not going to talk about these factors; this talk will only focus on the genetics.
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