What you should know about the APOE4 gene

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December 30, 2022 – Actor Chris Hemsworth in November announced that he was stepping away from acting to focus on his family and reassess his personal priorities. His decision was spurred on by discovering a genetic susceptibility to Alzheimer’s disease while working on itLimitless, a docuseries from National Geographic that focuses on ways to slow age-related decline. Hemsworth learned he has two copies of the APOE4 gene (one from each of his parents), which is known to increase the risk of Alzheimer’s.

Its discovery has brought new attention to the role of genes in Alzheimer’s disease. While there’s cause for concern, it’s nothing to worry about, says Howard Fillit, MD, co-founder and chief science officer of the Alzheimer’s Drug Discovery Foundation.

Yes, genetics can increase Alzheimer’s risk, but genes are not the same as fate, according to Fillit, who is also a clinical professor of geriatric and palliative care medicine and neuroscience at Mount Sinai School of Medicine in New York. The risk can be offset by things like living a healthy lifestyle.

What is the APOE4 gene?

One of the important functions of the protein apolipoprotein E (APOE), encoded by the APOE genes, “is to carry and be involved in cholesterol metabolism and to be involved in the repair of neurons in the brain,” explains Fillit. “It also performs many other functions, including binding to amyloid beta, which is involved in brain plaque formation and neuronal injury and has been linked to Alzheimer’s disease.”

The APOE4 gene codes for a mutated form of APOE and is one of the most important genetic risk factors for the development of Alzheimer’s disease. About 5% of the population has two APOE4 genes, and about 15% of the population carries one copy of the APOE4 gene, Fillit says.

Possession of two copies increases a person’s risk of Alzheimer’s by about 15%, and people with two copies can start showing symptoms 10 years earlier than the average person. But that doesn’t mean that anyone with two copies of the gene will definitely develop Alzheimer’s.

Genes can be “turned on” or “turned off.”

Although genetics can’t be changed, your risk can be reduced even if you have the APOE4 gene, notes Fillit.

The Lancet Commission on Dementia Prevention, Intervention, and Care identified 12 variable risk factors for the development of Alzheimer’s disease: low education, high blood pressure, hearing loss, smoking, obesity, depression, lack of exercise, diabetes, poor social contacts, excessive alcohol consumption, traumatic brain injury and air pollution. Taken together, these factors account for about 40% of dementia cases worldwide.

Research supports the role of a healthy lifestyle in improving thinking skills and memory in older adults with the APOE4 gene. Fillit points to the Finnish geriatric intervention study to Prevent Cognitive Impairment and Disability (FINGER), a clinical study conducted in six centers across Finland. It found that a healthy diet and management of vascular risk factors, as well as physical, cognitive, and social activities, helped slow cognitive decline, even in this high-risk population.

Uma Naidoo, MD, director of nutritional and lifestyle psychiatry at Massachusetts General Hospital in Boston, says that with the exception of certain congenital disorders, “our genes can affect ours risk developing a specific condition,” but these genes can be “turned on” or “turned off” depending on things like your environment, lifestyle, and age.

Brain Healthy Diet

Naidoo, who is also a faculty member at Harvard Medical School, emphasizes that a healthy diet can help stave off cognitive decline and dementia.

“As a Nutritional Psychiatrist, my work focuses on using healthy whole foods and nutrients to improve mental well-being as part of a healthy lifestyle with a holistic and integrated approach,” she says.

Optimizing our diet “can support a healthier mood and brain and reduce the inflammation associated with the neurodegeneration that underlies Alzheimer’s disease,” continues Naidoo, a professional chef, nutritional biologist, and author of the book This is your food brain.

Naidoo emphasizes the relationship between gut and memory.

“Although many factors play a role, it is important to understand that many of the chemicals that control the brain and body are regulated by the gut, and the composition of the gut bacteria is actually drastically different in patients with neurological disorders such as Alzheimer’s.” ”

Eating a nutrient-dense, anti-inflammatory diet that includes foods rich in probiotics can improve the gut microbiome — the bacteria in the gut — “in a way that resists the development and progression of Alzheimer’s,” says Naidoo.

Recent research points to the negative effects of ultra-processed foods on memory and dementia. The World Health Organization’s recommendations for lifestyle changes to prevent cognitive decline and dementia include a healthy diet rich in fruits, vegetables, legumes, nuts and whole grains with less than 30% of total calories from fat and less than 5 grams of salt . In particular, the WHO recommends a Mediterranean diet limited to red meat and whole dairy products and consuming only small to moderate amounts of alcohol.

Get more exercise

The WHO also recommends physical activity to reduce the risk of cognitive decline.

“Both aerobic and strength-training exercise have been associated with improved cognition and reduced cognitive decline in older adults,” says Belinda Brown, PhD, associate director of the Center for Healthy Aging at Murdoch University in Perth, Australia.

“Research also shows that aerobic exercise can increase brain volume, and there is growing evidence that yoga and tai chi may protect the brain later in life, probably in a different way than aerobic exercise,” says Brown , whose research focuses on understanding the role of lifestyle — particularly exercise — in maintaining a healthy aging brain and preventing cognitive decline and dementia. “Research suggests that physical activity may even counteract the negative effects of APOE4.”

“Exercise” encompasses a range of physical activities, including sports and planned exercises, walking, cycling, and even chores. The Alzheimer’s Association provides recommendations for staying safe and physically active.

The “sweet spot” of sleep

Much attention has been focused on diet and exercise to prevent or slow cognitive decline and dementia, but “as a society, we’re finally realizing the importance of sleep,” said Rebecca Robbins, PhD, a faculty member at Harvard Medical School in Boston.

“One of my favorite areas of sleep science is uncovering how important sleep is from our brain’s perspective,” she says. “When we get a healthy amount of sleep and a consolidated amount of sleep, not only do we wake up feeling better the next day, but sleep could also play a crucial role in the movement of dangerous toxic particles that build up in our brains learning new information.”

Studies have shown that the clearance of these toxic particles increases by 60% during sleep compared to waking hours. These particles contribute to the accumulation of beta-amyloid, explains Robbins, who is also a co-author of the book sleep for success.

There’s a “U-shaped relationship” between sleep and several negative outcomes, with too much sleep and too little being problems, she says.

“The best health and well-being is observed in people whose sleep duration is in the ‘sweet spot’ of 7 to 9 hours per night. All of this points to the hypothesis that sleep is central and a really important lifestyle factor to focus on when optimizing health and performance.”

Other lifestyle factors

To reduce your risk of Alzheimer’s disease, you need to address as many other risk factors as possible:

  • Stop smoking.
  • Reduce stress and treat depression; Mind-body approaches and psychotherapy may help.
  • Reduce exposure to air pollution.
  • Work with your doctor to manage conditions like diabetes, high blood pressure, high cholesterol, hearing impairment, and obesity.
  • Increase social and recreational activities and keep your brain active.

Who should get genetic testing?

Fillit does not advise routine genetic testing for Alzheimer’s disease.

“I would recommend it to patients with a strong family history of Alzheimer’s or if a younger person — let’s say someone in their 60s or younger — has memory loss or other symptoms of dementia.”

Getting tested is a very personal decision, he notes.

“Some people want to know their risk, some don’t. Some people might want to know if their children are at risk,” he says.

Having the information can be helpful if it is a motivation to make lifestyle changes.

“The value of getting tested, particularly in families with intergenerational Alzheimer’s disease in a parent, sibling, or grandparent, would be to ensure adherence to prevention programs, avoid risk factors, and receive advanced care planning, such as: For example, extended health guidelines and wills exist,” says Fillit.

See below for additional resources on lifestyle factors to improve brain health and prevent cognitive decline, as well as the role of genetics in Alzheimer’s risk.

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What you should know about the APOE4 gene
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