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It’s in a Gene—Or Is It?

The media has been abuzz with talk of what journalists have dubbed “the Alzheimer’s Gene,” and this has sent people scurrying to get a genetic test to see if they carry the gene. But putting aside the hype, is there really such as thing as “the Alzheimer’s Gene” and should you go and get yourself and your family members tested for it? It has long been known that dementia runs in families, and that if your parents developed Alzheimer’s later in life, you are very likely to develop it too. So, the question is not whether there is a genetic component to dementia, but rather, whether the risk for developing the disease can be narrowed down to one single “Alzheimer’s Gene.”

The gene that is getting all the attention in the media is called apolipoprotein E ε4, generally shortened to APOE4. It is actually a mutation—or variant—of the APOE gene. This gene controls the production of apolipoprotein E, a protein that transports cholesterol to neurons in the brain and assists in the clearance of amyloid-β, (the accumulation of which leads to the formation of amyloid plaques, which are now considered to be one of the causes of Alzheimer’s, as discussed in previous newsletters). Individuals with the APOE4 variant have been shown to have the highest levels of amyloid-β in their brains. Not surprising, APOE4 has been associated with late-onset Alzheimer’s in numerous studies and it therefore deserves closer examination. If you inherit APOE4 from one of your parents, your risk of developing Alzheimer’s increases by 2 or 3 times; if you inherit it from both parents, the risk increases by up to 12 times. However, it is important to note that there is no evidence yet that APOE4 causes Alzheimer’s. Some people who carry it do not get Alzheimer’s, while others who do carry it actually end up with the disease. There is a blood test that can tell you whether you carry APOE4, but it will not tell you whether or not you will get Alzheimer’s. APOE4 is not the only gene that has been identified as creating an elevated risk of developing dementia

In an earlier newsletter, we discussed the role that inflammation plays in the onset of Alzheimer’s. Scientists have now identified two genes associated with inflammation. CR1 is a major component of the immune system and is responsible for the regulation of inflammation as well as for the clearance of amyloid-β in the brain.

Variants of several other genes (PLD3, ABCA7, SORL1, and PICALM) have been found in a significant number of Alzheimer’s patients, though the exact roles of these genes in cognitive functioning are still not entirely clear. What is clear is that the genetic underpinnings of dementia, and Alzheimer’s in particular, are far more complex than is suggested by the popular notion of “the Alzheimer’s Gene.” Scientists are hard at work to understand this complexity, and future research will produce a more detailed picture of how genetics influences the cognitive decline that sometimes accompanies aging.

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