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Having a copy of ApoE4 gene variant doubles Alzheimer's risk for women but not for men

Having a copy of ApoE4 gene variant doubles Alzheimer's risk for women but not for men

brain cactus - smallSince the early 1990s, when Duke University neurologist Allen Roses, MD, first broke the news, it’s been known that a person carrying the gene variant known as ApoE4 is at elevated risk of getting Alzheimer’s disease. To this day ApoE4 is the strongest known single genetic risk factor for Alzheimer’s, a progressive neurological syndrome that robs its victims of their memory and reasoning ability.

But only now is it looking certain that the increased Alzheimer’s risk ApoE4 confers is largely restricted to women. Men’s fates don’t seem to be altered nearly as much by the genetic bad penny that is ApoE4, according to a new Annals of Neurology study led by Mike Greicius, MD, medical director of the Stanford Center for Memory Disorders.

Accessing two huge publicly available national databases, Greicius and his colleagues were able to amass medical records for some 8,000 people and show that initially healthy ApoE4-positive women were twice as likely to contract Alzheimer’s as their ApoE4-negative counterparts, while ApoE4-positive men’s risk for the syndrome was barely higher than that for ApoE-negative men.

What the heck is ApoE4 for, anyway? In my release on the new study, I wrote:

The ApoE gene is a recipe for a protein important for shuttling fatty substances throughout the body. This is particularly important in the central nervous system, as brain function depends on rapid rearrangement of such fatty substances along and among nerve cell membranes. The ApoE gene comes in three varieties — ApoE2, ApoE3 and ApoE4 — depending on inherited variations in the gene’s sequence. As a result, the protein that the gene specifies also comes in three versions, whose structures and fatty-substance-shuttling performance differ. Most people carry two copies of the ApoE3 gene variant (one from each parent). But about one in five people carries at least one copy of ApoE4, and a small percentage have two ApoE4 copies. Numerous studies … have confirmed that ApoE4 is a key risk factor for Alzheimer’s disease, with a single copy of ApoE4 increasing that risk twofold or fourfold. Carrying two copies confers 10 times the risk of Alzheimer’s.

Early hints in the medical literature that the ApoE4 variant exerted differential effects on women’s versus men’s brains were largely ignored until now, says Greicius. He says that’s because most of the seminal ApoE4/Alzheimer’s genetics research was conducted as case-control studies: The ApoE4 gene version’s frequency in people with Alzheimer’s was compared to its frequency in people without the disease. (About half of those with Alzheimer’s, but only about 15 percent without it, are positive for ApoE4.)

But that method has limitations, says Greicius: “About 10-15 percent of ‘normal’ 70-year-olds will develop Alzheimer’s if you wait five or ten years.” Their lurking in the “normal” group dilutes the results. Moreover, Greicius says,“these kinds of genetic studies are looking for needles in a haystack, so they require large numbers of subjects – thousands – to achieve statistical significance. If you want to further examine male/female differences, you have to double the sample size.” That’s costly.

And that’s how come the large government- and industry-supported repositories to which Greicius and his team resorted are such a great idea.

Previously: Estradiol – but not Premarin – prevents neurodegeneration in women at heightened dementia risk, Common genetic Alzheimer’s risk factor disrupts healthy older women’s brain function, but not men’s, Hormone therapy halts accelerated biological aging seen in women with Alzheimer’s genetic risk factor and A one-minute mind-reading machine? Brain-scan results distinguish mental states
Photo by Sean Michael Ragan

7 Responses to “ Having a copy of ApoE4 gene variant doubles Alzheimer's risk for women but not for men ”

  1. Joanne Says:

    Is there a test for APO4 existence and is it easily available?
    Thanks so much for your answer!


  2. Bruce Goldman Says:

    Joanne,tests that specifically test for the APOE4 gene variant have been available for quite some time, but have required a doctor’s signature. In addition, there are now several direct-to-consumer companies that test for hundreds of thousands (if not millions) of gene variants across the entire genome, including APOE4 and many, many others. Although these companies have, lately, been enjoined from making any comments about the medical implications of these variants, customers can still find out whether they have this or that one, and then research it on their own or via their physician.

  3. Etty Brunner Says:

    23andme is still in business and it has competitors, they all provide a complete genome test, but I haven’t tried it yet. I intend to discuss it with my doctor, I signed up for a “concierge medicine” doctor this year. It seems like regular doctors get more stressed and less effective as I get older. It wasn’t working for either me or the doc.

  4. Karen Says:

    If one discovers they do have the apoe4 gene is there anything one can do to lower the risk? Such as diet exercise?

  5. Moonya Says:

    I did have 23&me testing done just before the FDA required they stop giving medical results. I do know my status in terms of risk(SNP rs7412 CCe3/e4)
    and assume I should at least attempt to recognize early symptoms as well as watch me diet and keep my aerobic activity regular. My maternal line, mom, grandmother, great grandmother had AD, I’m guessing I will too one day, but hopefully not before we have some kind of a cure.

  6. Ralph Dorward Says:

    I find it rather disconcerting that many “reliable” sources of information on this subject, including the National Institute on Aging, do not mention this gender effect.

  7. Jeff in AZ Says:

    re: What to do if you have apoe4?

    Google the MEND protocol … Dr. Bredesen.


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