Is Alzheimer’s Hereditary?

Many different questions may keep you up at night as you watch a parent or sibling deteriorate as a result of Alzheimer’s disease—at first forgetting names and missing keys, then finally losing the ability to walk, talk, or even feed themselves. How much do they endure? Do they still recognize me? And let’s be real, what does this imply for me? Will I inevitably develop Alzheimer’s disease as well?

The best response may be, “It’s tricky,” as scientists continue to learn more about how specific characteristics and disease risks are handed down through the DNA we inherit from our parents.

A very tiny percentage of Alzheimer’s cases are caused by genetic abnormalities that are passed down through families and can result in a particularly severe form of the illness that strikes people in their prime. However, Alzheimer’s disease typically develops sporadically and may be triggered by a number of reasons.

According to James Noble, M.D., an associate professor of neurology at Columbia University Irving Medical Center, “there are about three dozen distinct genes that pose a slightly higher, or slightly lower, risk for persons acquiring Alzheimer’s.” He continues, “But even if you have one of those genes, it doesn’t imply you’re going to get the illness. The effects of the Alzheimer’s-associated genes vary in different racial/ethnic groups, and lifestyle factors like exercise, diet, and social involvement can also boost or lower a person’s risk.”

The distinction between Alzheimer’s disease with early and late onset

Based on the timing of the onset of cognitive impairment, two major groups of Alzheimer’s disease can be distinguished. Age is the main risk factor for late-onset Alzheimer’s, which often manifests beyond the age of 65. In actuality, the chance of getting Alzheimer’s rises dramatically with age: The average person has a one in three risk of having the disease by the age of 85.

Dr. Noble says that when Alzheimer’s runs in families, “it may sometimes be more visible because there is longevity in that family.” “It may be that longevity has a similar or higher influence than genetics in those families if someone has parents and grandparents who live to reach 90 and those people have Alzheimer’s disease.”

Early-onset (or young-onset) Alzheimer’s disease occurs when symptoms start to develop before the age of 65, even as early as in a person’s 30s. This type of Alzheimer’s accounts for less than 10% of all cases. Although early-onset Alzheimer’s disease can also be sporadic (occurring without a documented family history), in rare circumstances it may be brought on by a particular, inherited genetic abnormality.

What genes put you at higher risk for Alzheimer’s disease?

Numerous genes may influence your risk of acquiring Alzheimer’s, according to researchers. Once more, these genes merely push the odds in one direction rather than determining whether you will actually develop Alzheimer’s. The APOE-e4 gene, which is thought to be present in 40 to 65% of patients with Alzheimer’s disease, is the most well-known and extensively researched of these “risk genes.”

There are three distinct alleles (or variants) of the APOE gene, including e2, e3, and e4. Everyone receives one APOE gene from each of their parents. A single copy of the APOE-e4 gene increases your chance of Alzheimer’s disease by thrice; two copies can increase your risk by up to eight to ten times (the Alzheimer’s Association estimates that just 2% of Americans have two copies of the gene).

On the other side, your risk of Alzheimer’s decreases if you inherit the APOE-e2 variant. The most prevalent APOE allele, e3, is thought to have little bearing on the likelihood of developing Alzheimer’s disease. According to Dr. Noble, there are a variety of other factors, such as socioeconomic factors that affect health, that are linked to APOE gene expression, including race. “We know from many studies that e4 seems to have a higher risk of expressing Alzheimer’s in non-Hispanic white people, while it appears to have a lower impact on those who are non-Hispanic Black people,” he explains.

Also keep in mind that even if you do carry one of these genes, your risk of Alzheimer’s only rises proportionately with age. For instance, the prevalence of Alzheimer’s disease in Americans aged 65 to 74 is thought to be 3%. Therefore, even if genetics causes your risk to increase threefold, you still only have a 9% chance of having it at that age.

Genes linked to hereditary Alzheimer’s.

While receiving risk genes like APOE-e4 and others only increases the likelihood that someone will get Alzheimer’s, there are a very small number of extremely uncommon situations in which inheriting a “deterministic gene” ensures that someone will virtually certainly get Alzheimer’s. These represent less than 1% of all instances of Alzheimer’s and are only known to have an impact on a small number of extended families globally. Early-onset familial Alzheimer’s disease, or EOFAD, is a form of Alzheimer’s that often affects family members who inherit the gene in their 40s or 50s. Each offspring has a 50/50 chance of inheriting this genetic mutation if one parent carries it.

Three genes, the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2), each located on a different chromosome and each linked to an excessive production of beta amyloid proteins in the brain, a defining feature of the disease, have so far been linked to early onset Alzheimer’s. According to Dr. Noble, “These genes only account for a small portion of those who have the condition overall.” Many persons with early-onset Alzheimer’s disease do not have a family history, and some early-onset families lack a gene that can be identified.

How do genetics impact medical care?

According to Dr. Noble, until recently, the only FDA-approved drugs for Alzheimer’s disease primarily addressed the disease’s symptoms rather than its underlying pathology. As a result, genetics had no bearing on the choice of a treatment. Adulhelm (aducanumab), the first medication created to slow the progression of the disease in people with mild cognitive impairment by preventing the formation of beta-amyloid plaques in the brain, received FDA approval in June 2021. However, it is still unclear whether the contentious medication can actually slow the disease’s progression, and some prestigious hospitals are refusing to provide the treatment. According to Dr. Noble, people with the APOE-4 gene were more likely than people without that variant to encounter medication adverse effects during clinical trials. He clarifies, “It’s not that those folks can’t use the substance; it’s just something we have to keep on our radar.

According to Dr. Noble, the only other circumstance in which genetic testing might affect treatment is if it turns out that the patient actually has frontotemporal dementia (FTD) rather than a genetic variant of early-onset Alzheimer’s. Since certain FTD patients may not respond well to the drugs for Alzheimer’s, other treatment regimens may be used in those situations.

Should You have an APOE-e4 z test?

You’ve definitely seen advertisements for genetic test kits that can not only identify your long-lost relatives but also determine your susceptibility to specific diseases. The APOE-e4 gene can be found with these tests, which you may perform at home or at a medical facility, but they cannot tell you whether you will eventually acquire Alzheimer’s disease. Due of this, a large number of professionals and advocacy organizations, such as the Alzheimer’s Association, advise clients to only undergo genetic testing after giving it careful thought and under the supervision of a genetics counsellor who can put the danger in context.

Dr. Noble adds that although the decision to get tested is very personal, it’s crucial to be aware of the consequences. “You need to consider how you’re going to use the information. What potential advantages and disadvantages exist? How will this affect the rest of my family members? The Genetic Information Nondiscrimination Act (GINA) of 2008 made it illegal for medical insurance providers to discriminate based on genetic testing, but it does not apply to long-term care insurance or disability insurance, according to Dr. Noble. As a result, it is possible that your results may affect your ability to obtain coverage for your care should you become disabled.

The conclusion

Your genes are only one part of your narrative, according to Dr. Noble, even while we are learning more and more every day about how the genes we inherited from our parents increase our risk for Alzheimer’s disease. Only in extremely rare instances do genetics turn out to be the reason why a specific person develops Alzheimer’s disease, according to him. “Genetics can provide us a deeper understanding of the pathobiology of disease and give us guidance as we study novel treatments,” he says.

No matter your genetic makeup, the only thing you can do is adhere to the recommendations for reducing your risk for all dementias, which include regular physical activity, a Mediterranean or DASH diet, learning new things, engaging in social activities, managing your blood pressure, and maintaining overall cardiovascular health.

Dr. Noble advises his patients who appear to have a higher genetic risk for Alzheimer’s to do that. But then again, no matter their genetic profile, that’s what we would advise anyone, he adds.

Also Read ABout How Is Alzheimer’s Disease Treated?