Recent genetic research has highlighted the significant risk associated with inheriting two copies of the APOE4 gene variant, with studies indicating that approximately 60% of individuals with this genotype will develop Alzheimer’s disease by the age of 85.
Despite the alarming statistics, only a small percentage, ranging from 2% to 3% of the U.S. population, actually carries two copies of the APOE4 variant. Many remain unaware of their genetic predisposition due to a lack of genetic testing.
Among those who know their status are three distinguished scientists, each of whom has made a commitment not only to protect their own cognitive health but also to advocate for the broader community affected by the APOE4-4 genotype.
**June: From Dismay to Hope**
In 2023, June, who requested anonymity for personal reasons, received unsettling news from a 23andMe genetic test that confirmed her status as an APOE4-4 carrier.
At 57 years old, she felt devastated. As a biochemistry expert, June quickly grasped the implications of her results, realizing that individuals with her genetic makeup often experience symptoms of Alzheimer’s much earlier than the general population.
The gravity of her situation initially led her to spend sleepless nights conducting extensive online research about Alzheimer’s and its genetic factors. Faced with the daunting prospect of deteriorating health, June even contemplated physician-assisted suicide to avoid burdening her adult son.
However, her outlook shifted after discovering supportive online communities such as ApoE4.info, where she found not just valuable information but also built meaningful connections with others sharing her genetic profile.
Through these interactions, June learned about brain healthy practices, including the Mediterranean diet, regular exercise, quality sleep, and techniques for stress management.
While browsing the Alzheimer’s Association website, she stumbled upon a promising research project from the University of California, San Diego (UCSD), investigating the positive effects of rigorous mental and physical exercises on brain health for individuals aged 50 to 85.
In 2024, June joined the study, engaging in challenging activities, such as cycling through virtual reality environments that required significant cognitive engagement.
The research included numerous MRI scans and cognitive evaluations, which proved to be transformative for her.
“I not only got to watch my brain in action, but I was also able to formulate effective memory retention strategies,” June explained.
Her participation in the study ignited a passion for advocacy, leading her to push for federal funding for Alzheimer’s research and urging the Food and Drug Administration (FDA) to consider treatments that could benefit those with the APOE4-4 genotype.
Reflecting on her journey, June stated, “I realize that being APOE4-4 is not the end of the world. There’s so much we can do.”
**David Watson: Focused on Drug Discovery**
A blend of physical and mental activity can help delay Alzheimer’s symptoms, according to David Watson, a neuropsychologist and CEO of the Alzheimer’s Research and Treatment Center in Florida.
However, Watson acknowledges that lifestyle changes alone do not counteract genetic predispositions.
In his mid-50s, he discovered his genetic status over 25 years ago, spurred by witnessing several family members develop Alzheimer’s disease. Watson chose to dedicate his career to clinical trials aimed at uncovering new Alzheimer’s drugs that could offer protection for his brain.
His work has been instrumental in bringing to market two novel medications, lecanemab and donanemab. Unfortunately, Watson himself is not a suitable candidate for either treatment due to the associated risks of brain swelling or bleeding linked to his genetic profile.
He advises caution, stating, “If someone is APOE-4-4, they should probably not go on a monoclonal antibody targeting amyloid. If they do, it should be very cautiously with additional counseling.”
Instead, Watson has turned his attention to an experimental drug specifically intended for individuals carrying two copies of the APOE4 variant.
This innovative oral medication, developed by Alzheon, aims to disrupt the formation of amyloid plaques in the brain rather than simply removing existing ones.
Watson shared promising results from early trials of this drug, highlighting that it did not induce brain swelling or bleeding and appeared to prevent the areas of the brain responsible for memory from shrinking, which is a common symptom of Alzheimer’s.
Although a larger trial failed to conclusively demonstrate the drug’s efficacy in slowing cognitive decline in those who already exhibited Alzheimer’s symptoms, Watson remains optimistic.
He noted that some participants who continued on the drug seemed to maintain their cognitive abilities, saying, “We’re really making a difference in keeping neurons alive.”
**Wendy Nelson: Going Very Public**
In 2022, Wendy Nelson’s genetic test from 23andMe revealed her own APOE4-4 status, prompting initial silence.
The 54-year-old PhD scientist in the biotech industry was well aware of the implications her results carried but felt uncertain about how to navigate her situation.
Wendy was already engaged in activities promoting brain health; she identified herself as a triathlete and a dedicated hiker who enjoys a healthy diet.
Upon learning of her genetic risk, the primary changes she made included quitting alcohol and starting medication to manage cholesterol.
Then, a connection within the biotech field introduced her to a podcast focused on dementia and brain health, which led to her first interview.
At that time, no one knew her genetic status, and Nelson thought, “Who’s ever going to see this?”
To her surprise, the interview garnered significant attention, leading to more podcast features, a Reuters interview, and appearances on television news.
She soon found herself working with advocacy groups, including the APOE4-4 Alzheimer’s Alliance, aiming to raise awareness regarding her genetic profile and its implications.
For Nelson, being a public advocate for the APOE4-4 community provides a platform to educate the public about the genetic risks and advocate for further research into Alzheimer’s treatment options.
Just weeks ago, she had the opportunity to address officials at the FDA, sharing her testimony and urging for more treatment options tailored for individuals with her genetic makeup.
“I provided my seven minutes of testimony to the FDA, which was my plea for more options,” she expressed.
“I don’t feel like I have anything out there right now.”
image source from：npr
