Amyloid and Alzheimer’s: How Genetics and Lifestyle May Affect Dementia Risk
When assessing your risk for cardiovascular disease, you know to pay close attention to your cholesterol levels. More LDL (“bad”) cholesterol is associated with a greater risk of plaque buildup in your arteries, increasing your odds of having a heart attack or stroke or developing conditions such as peripheral artery disease.
Similarly, the buildup of beta-amyloid plaques in the brain is associated with a greater risk of Alzheimer’s disease (AD). Betaamyloid, often referred to simply as “amyloid,” is a type of protein that can form clumps or plaques in the brain, disrupting communication between brain cells (neurons) and triggering neuroinflammation—a condition that sets the stage for AD and other types of dementia.
But unlike cholesterol, which can often be controlled through lifestyle modifications and statin therapy, amyloid buildup is a more complicated and challenging health problem to manage. One reason is that an individual’s risk for amyloid accumulation can be greatly influenced by genes that predispose a person to abnormal amyloid buildup.
Though variants of many genes are associated with amyloid buildup, the APOE4 gene is among the most significant and well-studied when it comes to AD risk. It’s associated with a higher density of amyloid plaques. Inheriting one copy of the APOE4 gene increases your AD risk threefold (compared with not having the gene), while inheriting two copies increases your AD risk by about 14 fold, says Alzheimer’s researcher Rudolph Tanzi, PhD, director of the Genetics and Aging Research Unit at Massachusetts General Hospital (MGH) and co-director of the Henry and Allison McCance Center for Brain Health at MGH.
For those reasons, Dr. Tanzi suggests individuals with a known genetic risk should prioritize managing the AD risks that are within their control. That includes regular exercise, a plant-based diet, and mental stimulation. “If you have one or two copies of APOE4, incorporating those steps in your life goes from a good idea to almost obligatory,” he says. He adds that just as it’s better to target cholesterol control earlier in your life rather than later, when arterial plaques have formed and put you at risk for heart disease, it’s worth giving amyloid buildup that same attention throughout your life.
Is Genetic Testing Right for You? A study published earlier this year in Nature Communications garnered a lot of media attention, as it reaffirmed the risks associated with inheriting two copies of APOE4. It also prompted a lot of discussion about genetic testing.
Should you be tested for the APOE4 gene or any of the others associated with AD risk? This is the million-dollar question, and the right answer depends on the individual, and often that person’s family, too. You can find out, through testing, whether you’ve inherited one or two APOE4 genes or whether you’ve escaped that genetic misfortune. But if you get an answer you don’t want, what then?
“Do you really want to know?” Dr. Tanzi says. “And do you want your kids to live with that stress? It’s a pretty big decision.” Often, people are advised to consider genetic testing if they have a family history of early-onset AD, generally considered to be AD that takes hold before the age of 60. An individual who develops early-onset AD may also want to be tested, even if there is no known family history of the disease.
Attacking Amyloid
As concerning as amyloid is, Dr. Tanzi notes that amyloid buildup does not guarantee that AD will follow. Research has shown that people can have a significant amount of amyloid in the brain, but have no AD symptoms.
One reason, Dr. Tanzi explains, is that there can be a lag of many years between the accumulation of amyloid in the brain and the development of neuroinflammation and subsequent AD. Other studies have shown that some people who preserve cognitive health despite the presence of amyloid plaques have a unique protein makeup within their synapses (connections between neurons) that may offer some protection.
Rather than take a chance that you’ll be spared the potential complications of amyloid plaques in the brain, you may want to follow some basic lifestyle behaviors that may help prevent amyloid buildup and reduce your risk for AD. Dr. Tanzi refers to these behaviors with the acronym SHIELD.
• Sleep: While you sleep, your brain can clear out some amyloid.
• Handle stress: “Stress causes cell death, which activates neuroinflammation,” Dr. Tanzi says.
• Interact with others: Interacting with other people on a regular basis stimulates the brain to create new brain cells, a process called neurogenesis.
• Exercise: “Exercise induces neurogenesis. Think of it as getting your reserves in place,” says Dr. Tanzi. He adds that exercise also triggers the muscles to produce a hormone called irisin, which in turn induces the release of an enzyme called neprilysin, which helps break down amyloid in the brain.
• Learn new things: Like socializing, learning fosters the production of new neurons and strengthens the synapses, Dr. Tanzi says.
• Diet: “If your microbiome is healthy in your gut, it will help reduce amyloid and reduce neuroinflammation,” Dr. Tanzi explains.
Blood sample for ATN (Amyloid-Tau-Neurodegeneration) profile test, to diagnosis of Alzheimer’s disease. Alzheimer’s test.
Your microbiome is the collection of all bacteria, fungi, and other microorganisms and their genes living inside and outside of your body. Studies have demonstrated a strong connection between gut health and brain function. Dr. Tanzi’s research and that of others suggests that a plant-based diet may be optimal for a healthy gut microbiome and, by extension, better brain health.
Takeaway
As with so many diseases and medical conditions, AD can develop through a combination of genetic, environmental, and lifestyle factors. While you can’t control the genes you inherit, you can pursue the lifestyle behaviors that appear to offer some protection.
And, of course, regular exercise, a balanced diet, mental stimulation, good sleep, and stress management won’t just help protect against dementia. Those traits make up the recipe for good overall health and well-being.
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