People who inherit two copies of a gene variant called APOE4 have a 60% chance of developing Alzheimer\u2019s by age 85.\n<\/p>\n
Only about 2% to 3% of people in the U.S. have this genetic profile, and most of them don\u2019t know it because they\u2019ve never sought genetic testing.\n<\/p>\n
But three scientists are among those who did get tested, and learned that they are in the high-risk group. Now, each is making an effort to protect not only their own brain, but the brains of others with the genotype known as APOE4-4.\n<\/p>\n
June: from dismay to hope<\/p>\n
A genetic test from 23andMe gave June the bad news in 2023.\n<\/p>\n
\u201cI just felt like the end of the world,\u201d says June, who asked to use only her first name out of fear that making her genetic status public could affect her job or health insurance.\n<\/p>\n
June was 57 when she found out. As someone with a doctorate in biochemistry, she quickly understood what the results meant.\n<\/p>\n
\u201cPeople with our genotype are almost destined to get the disease,\u201d she says. \u201cWe tend to get symptoms 7 to 10 years earlier than the general population, which means that I had about seven years left before I may get the disease.\u201d\n<\/p>\n
At first, June spent sleepless nights online, reading academic papers about Alzheimer\u2019s and genetics. She even looked into physician-assisted suicide in an effort to make sure she would not become a burden to her adult son.\n<\/p>\n
Then she discovered online communities like ApoE4.info<\/a>, which included people with her genetic profile.\n<\/p>\n \u201cI not only found useful information, I forged deep friendships with people,\u201d she says.\n<\/p>\n June learned about the brain benefits of a Mediterranean diet, exercise, sleep, and stress reduction. And while perusing the Alzheimer\u2019s Association<\/a> website, she discovered an intriguing research project at the University of California, San Diego.\n<\/p>\n It\u2019s an ongoing study<\/a> to see whether four months of vigorous mental and physical exercise can improve brain health in people ages 50 to 85.\n<\/p>\n So in 2024, June found herself on a stationary bicycle at UCSD playing a strenuous virtual reality game.\n<\/p>\n \u201cYou\u2019re riding a bike and you go through unfamiliar terrain where you need to make turns,\u201d she says. \u201cSo you really have to use all your cognitive reserve.\u201d\n<\/p>\n The study also involved a series of MRI scans and cognitive tests.\n<\/p>\n \u201cThat was absolutely a game changer because I not only got to watch my brain in action, I was able to develop really effective strategies of retaining my memory,\u201d she says.\n<\/p>\n Since participating in that trial, June has been advocating for federal funding for Alzheimer\u2019s research and urging the Food and Drug Administration to consider drugs that might benefit people who have the APOE4-4 genotype.\n<\/p>\n \u201cI realize that being APOE4-4 is not the end of the world,\u201d June says. \u201cThere\u2019s so many things we can do.\u201d\n<\/p>\n David Watson: drug discovery<\/p>\n Lots of mental and physical activity might delay the symptoms of Alzheimer\u2019s, says David Watson<\/a>, a neuropsychologist and CEO of the Alzheimer\u2019s Research and Treatment Center in Florida.\n<\/p>\n But that\u2019s not enough for him and other people who carry two copies of APOE4 variant.\n<\/p>\n \u201cAny of these things that we can do preventively, they\u2019re going to be helpful,\u201d Watson says. \u201cBut are they going to override genetics? No, they\u2019re not, unfortunately.\u201d\n<\/p>\n Watson, now in his mid 50s, learned his genetic status about 25 years ago after seeing several family members develop Alzheimer\u2019s.\n<\/p>\n He decided to devote his career to running clinical trials of Alzheimer\u2019s drugs in hopes of finding one that might protect his brain.\n<\/p>\n That effort helped get two new drugs (lecanemab<\/a> and donanemab<\/a>) on the market. Unfortunately, Watson is not a good candidate for either drug.\n<\/p>\n Lecanemab and donanemab are both monoclonal antibodies that remove sticky amyloid plaques from the brain \u2014 a hallmark of Alzheimer\u2019s. But in people with Watson\u2019s genetic profile, the drugs often cause dangerous swelling or bleeding in the brain.\n<\/p>\n \u201cIf someone is APOE-4-4, they should probably should not go on a monoclonal antibody targeting amyloid,\u201d he says. Or if they do, it should be \u201cvery cautiously with additional counseling,\u201d he says.\n<\/p>\n So Watson has been focusing on an experimental drug<\/a> that\u2019s meant specifically for people with two copies of APOE4. The pill, which was tested in some patients at his center, is designed to interrupt the process that leads to amyloid plaques, rather than removing plaques that have already formed.\n<\/p>\n \u201cThis particular compound actually showed remarkable findings,\u201d Watson says.\n<\/p>\n The drug, made by Alzheon, didn\u2019t cause brain swelling or bleeding. And it prevented brain areas associated with memory from shrinking the way they usually do in Alzheimer\u2019s.\n<\/p>\n But in a large trial<\/a>, the drug failed to clearly show it could slow down cognitive decline in people who already had Alzheimer\u2019s symptoms.\n<\/p>\n Even so, Watson thinks the Alzheon drug has potential.\n<\/p>\n Some study participants who\u2019ve stayed on the drug seem to be \u201cholding their own\u201d instead of getting worse, Watson says. And blood tests of these participants suggest that \u201cwe\u2019re really making a difference in keeping neurons alive,\u201d he says.\n<\/p>\n Wendy Nelson: Going very public<\/p>\n When a genetic test from 23andMe showed that Wendy Nelson carried two copies of the APOE4 variant, she went quiet.\n<\/p>\n \u201cI just sort of didn\u2019t want to tell anybody at first,\u201d she says. \u201cI really just kept the results to myself.\u201d\n<\/p>\n Nelson, 54, is a PhD scientist in the biotech industry. So she knew what the results meant. But she didn\u2019t know what to do with them.\n<\/p>\n She was already taking part in the sort of activities that might protect her brain. \u201cI\u2019m a triathlete, a hardcore hiker, I eat healthy,\u201d she says.\n<\/p>\n So when she learned her status in 2022, about the only changes she could make were to stop drinking and start a cholesterol drug.\n<\/p>\n Then, one of Nelson\u2019s biotech contacts put her in touch with a podcast<\/a> about dementia and brain health. They asked her to do an interview. She agreed.\n<\/p>\n \u201cThat was at the point where no one knew what my status was,\u201d she says. \u201cBut in my mind, I was thinking, well, who\u2019s ever going to see this?\u201d\n<\/p>\n Lots of people, it turned out.\n<\/p>\n