Whilst unclear what role genetics play in the onset and development of Alzheimer’s disease in later life, previous research has suggested that those with a specific gene known as ApoE-4, may have an increased risk of developing the disease.
The ApoE gene, shorthand for the Apolipoprotein E, is a major cholesterol carrier that supports fat transport and injury repair in the brain. There are different forms of the ApoE gene (type 1-4), but not everyone has it and it also doesn’t seem to be required for normal brain function.
Previous research has found that people who develop Alzheimer’s disease are more likely to have the ApoE-4 gene, compared with those carrying the more common ApoE-3 gene. It has also been noted that those with ApoE-2 gene might have a decreased risk of Alzheimer’s disease.
Why is the ApoE-4 gene bad?
It is not yet fully known, but it has been shown that it can increase amyloid beta production in the brain, which is a hallmark sign of Alzheimer’s disease. Although it has never really been suggested that having the ApoE-4 gene will lead to Alzheimer’s disease, it is considered a risk factor – similar to how poor nutrition, lack of exercise, etc are also considered risk factors.
Researchers from the Washington University School of Medicine were keen to find out more about the role ApoE-4 in Alzheimer’s disease. In their study published in the journal Nature, they found mice genetically modified with the human form of ApoE-4 did have increased brain damage, but noticed it was actually being caused by Tau toxic tangles, not just amyloid beta clumps.
They also found mice without the ApoE gene did still develop the tau tangles, but it did very little harm to their brain cells.
“What we found was that when ApoE is there, it amplifies the toxic function of tau, which means if we can reduce ApoE levels we may be able to stop the disease process,” said study leader Dr David Holtzman from the University of Washington.
The researchers then went one step further and tested the effects of all four variants of the ApoE gene on Tau production and brain cell death.
This is where results start to differ from what we currently know. The researchers found that mice carrying any forms of the ApoE gene (i.e. 1-4) had some level of brain damage. However, mice with the ApoE-4 gene exhibited the most severe neurodegeneration, and mice with the ApoE2 gene, the least.
To make things interesting, the mice that lacked the ApoE gene entirely showed virtually no brain damage.
Since, ApoE doesn’t seem to be required for normal brain function, the researchers now hypothesise that targeting the ApoE gene and stopping its action could potentially halt neurodegeneration in later life.
This is something that has never been tested before and the researchers are keen to find out if it could work. As of yet, the research hasn’t progressed past an idea so we’ll keep an eye on how it progresses.
To read more about the study visit the link here