Individuals with two copies of the APOE4 gene variant have a 60% likelihood of developing Alzheimer’s by the time they reach 85. Surprisingly, this genetic profile is present in only 2% to 3% of the U.S. population, and most people are unaware of it since they haven’t pursued genetic testing.
Three scientists, however, took that step and discovered they belong to the high-risk category. Now, they are focused not just on their brain health but also on aiding others with the same APOE4-4 genotype.
In 2023, a 23andMe genetic test delivered distressing news to a woman named June. “It felt like the end of the world,” she recalls, using her first name due to concerns about job and insurance implications. With a PhD in biochemistry, she quickly comprehended the severity of her results.
June knew that those sharing her genetic makeup typically begin showing symptoms 7 to 10 years earlier than the broader population, which made her feel she had only about seven years left before her potential diagnosis. Initially, she spent sleepless nights pouring over research on Alzheimer’s and genetics, even considering physician-assisted suicide to avoid becoming a burden to her son.
Eventually, June stumbled upon online communities like ApoE4.info, connecting with others like her. “I found not just valuable information, but also deep friendships,” she explains.
Through these networks, she learned about the cognitive benefits of a Mediterranean diet, regular exercise, adequate sleep, and managing stress. Interestingly, she discovered a study at the University of California, San Diego, examining whether vigorous mental and physical activities could enhance brain health in individuals aged 50 to 85.
In 2024, June found herself pedaling away on a stationary bike in a virtual reality game as part of the study, emphasizing the need for cognitive engagement. “Navigating unfamiliar terrain required full cognitive engagement,” she shared.
The trial also included MRI scans and cognitive evaluations, which June found transformative. “It allowed me to see my brain at work and helped me develop effective memory retention strategies,” she adds.
After participating in the study, June began advocating for federal funding for Alzheimer’s research and appealed to the FDA for drug options for those with the APOE4-4 genotype. “Being APOE4-4 isn’t the end. There are so many proactive steps to take,” she asserts.
On the drug discovery front, neuropsychologist David Watson emphasizes that while mental and physical activity may delay Alzheimer’s symptoms, these won’t completely negate genetic predispositions. Watson, who learned about his genetic status two decades ago, is passionate about running clinical trials to find brain-protecting drugs.
Watson has been involved in bringing two drugs, lecanemab and donanemab, to market. Although both target amyloid plaques associated with Alzheimer’s, people with his genetic profile experience severe side effects from them. He cautions, “Those with the APOE4-4 variant should approach monoclonal antibody treatments with extreme caution.”
As an alternative, he is focusing on an experimental drug specifically designed for those with two copies of the APOE4 variant. Early results have been promising, as those who remained on the drug showed signs of maintaining their cognitive health.
Next, we meet Wendy Nelson, who similarly faced a tough reality upon discovering she carried two copies of the APOE4 variant through 23andMe. Initially, she kept this information to herself, unsure of how to navigate her new reality, despite already leading an active lifestyle.
After a series of podcast interviews, Nelson found herself advocating publicly for the APOE4-4 community. She became a vocal supporter for more research and even had the opportunity to testify before the FDA about the need for additional drug options. “I desperately want more options,” she shares, underscoring her commitment to pushing for change in the scientific landscape.
Through her public advocacy, alongside June and Watson, Nelson is helping to push for increased research efforts and a more streamlined regulatory process for new treatment options for those affected by the APOE4-4 genetic variant.
