Genes and Alzheimer's Disease

Image Credit: Disney Plus 

Chris Hemsworth's announcement on his health condition in his new show “a mission to live better for longer” on Disney Plus came like a bolt from the blue. The 39-year-old “Thor” Hollywood star discovered that he had a rare genetic combination of 2 copies of the APOE4 gene, which is associated with an increased risk of Alzheimer's disease. According to a 2021 study by the National Institutes of Health, APOE4 is the highest risk factor gene for Alzheimer’s disease, yet inheriting ApoE4 does not guarantee to develop the disease. 

Diving into “Memory Loss” Disease 

There are many different types of dementia, but Alzheimer’s disease is the most prevalent type with more than 55 million people with dementia, and approximately 10 million new cases reported annually. In Malaysia, 8.5% of elderly over the age of 60 are diagnosed with Alzheimer's disease, which becomes more common as we grow older.

Risk factors 

The causes of Alzheimer's Disease are still poorly understood by scientists and are probably due to several factors, each of which can affect a person differently. 

1. Increasing age
   Most important aspect is age. After reaching the age of 65, the risk of getting Alzheimer’s disease doubles every 5 years. However, anyone can be at risk for getting Alzheimer’s disease. 1 in 20 individuals under the age of 65 are living with this disease. People as young as 40 years old can develop this type of Alzheimer’s disease, often known as early or young-onset Alzheimer’s disease. 

2. Family history- Alzheimer’s disease comes in two different forms- early onset and late onset. Genetics play a role in both types. Further explanation about genes can be explored below! 

3. Down’s syndrome
   People with Down’s syndrome are more susceptible to develop Alzheimer’s disease. Because some people may develop Alzheimer's disease as a result of the genetic abnormalities that cause Down’s syndrome can also cause amyloid plaques to accumulate in the brain over time. 

4. Head injuries
   It’s possible that people who have suffered serious head injuries are more likely to develop Alzheimer’s disease. But more research is required in this area. 

5. Cardiovascular disease
   According to research, several illnesses and lifestyle choices linked to cardiovascular disease can increase the risk of Alzheimer's disease. These include smoking, diabetes, obesity, high blood pressure, and high cholesterol. 

6. Other risk factors
   Risk factors such as hearing loss, untreated depression, social isolation, sedentary lifestyle may be significant, albeit this does not necessarily imply that these factors directly contribute to dementia.   

Signs and symptoms 

Memory problems are the initial warning signs of Alzheimer’s disease and related dementia. Other symptoms may include: 

1. Memory loss that interferes with daily life. For instance, asking the same questions repeatedly or getting lost in a familiar setting

2. Difficulty managing finances and paying bills.

3. It may be a challenge to complete routine duties at work, at home, or in leisure.

4. Decreased or bad judgment.

5. Losing things easily and not being able to find them.

6. Mood, attitude, or behavior changes.

Even if you or someone you know exhibits many of these symptoms, it doesn't necessarily indicate that you have Alzheimer's disease.
 

How are genes related to this disease? 

You may wonder how genes are related to this disease? 

Although the actual increase in risk is minimal, the genes you inherit from your parents may increase your risk of having Alzheimer's disease. The probability of passing on the disease is substantially higher in families where Alzheimer's disease is caused by the inheritance of a single gene. 

There are 2 types of Alzheimer’s disease: 

1. Late-onset Alzheimer's disease- which typically manifest symptoms in person in their mid-60s and beyond

2. Younger or early onset Alzheimer's disease- rare and occurs among people in their 30s and mid-60s. 

Late-onset Alzheimer's disease

No unique gene has been identified as the direct cause of late-onset Alzheimer's disease. However, a person’s risk is increased by possessing a genetic variant of the apolipoprotein E (APOE) gene on chromosome 19. APOE gene is involved in producing a protein that aids in transporting cholesterol and other types of fat in the bloodstream. There are numerous alleles, or variations, of APOE. Two APOE alleles are inherited by each person, one from each biological parent. 

1. APOE 2 is comparatively uncommon and may offer some disease protection. This allele typically causes Alzheimer's disease to appear later in life than it would in someone with the APOE4 gene.

2. The most prevalent allele of APOE, 3, is thought to have no effect on Alzheimer's disease. 

3. APOE 4 is linked to an earlier age of illness onset and an increased risk for Alzheimer's disease. Alzheimer's disease risk is increased by having one or two APOE 4 alleles. Approximately 25% of persons have one copy of APOE-4, while 2% to 3% have two copies.

4. APOE 4 is referred to as a risk-factor gene because it increases the risk of developing the disease. But it is not guaranteed that a person inheriting APOE 4 allele would definitely develop Alzheimer's disease.  

Early-Onset Alzheimer's Disease

The following three single-gene mutations are linked to early-onset Alzheimer's disease: 

1. Amyloid precursor protein (APP) on chromosome 21

2. Presenilin 1 (PSEN1) on chromosome 14

3. Presenilin 2 (PSEN2) on chromosome 1

Mutation in these genes causes abnormal proteins to be produced. Each of these mutations contributes to the breakdown of APP, a protein that is part of a process that generates damaging amyloid plaques, a hallmark of Alzheimer’s disease.

While a blood test can reveal which APOE alleles a person carries, it cannot predict whether or not that person will go on to acquire Alzheimer's disease. You may wish to seek genetic counseling to learn more about chances of developing Alzheimer's disease in the future if several of your family members have experienced dementia over the generations, especially while they were young. 

Is there a cure? 

There is no cure for Alzheimer’s disease. Nonetheless, there is growing evidence that people who adopt healthy lifestyle practices such as routine exercise and blood pressure control can lower the risk of dementia. Healthy lifestyle choices which have been linked to lower risks for heart disease, diabetes and cancer may also lower the risk of subjective cognitive decline. 

1. Sleep
   Improving sleep by practicing good sleep hygiene of 7 yo 9 hours of sleep daily for healthy adults as recommended by the National Sleep Foundation guidelines. 

2. Regular exercise
   Exercising several times a week for 30 to 60 minutes can help maintain our capacity for thought, logic and learning. 

3. Social engagement
   A study shows that participation in social activities may minimize the risk of dementia due to mental and intellectual stimulation. Increased social engagement may also enhance our immune system and slow cognitive aging by improving cognitive function and enhancing positive emotional traits such as social skills and self esteem. Numerous studies suggest that preserving healthy social networks and remaining cognitively engaged as we age may reduce our chances of cognitive deterioration and Alzheimer's. 

4. Diet and Nutrition
   The phrase 'You Are What You Eat'  is true! Start by eating a healthy balanced diet consisting of vegetables, fruits, lean protein food, low fat dairy products and whole grains. A study has shown that eating a daily serving of leafy green vegetables such as kale and spinach is also associated with slower age-related cognitive decline. Incorporating brainy food into your meal plans including fatty fish, blueberries, turmeric, and almonds enhance your mood, hone your memory and support optimal brain function! Here is a list of ingredients of the MIND Diet (Mediterranean–DASH Intervention for Neurodegenerative Delay) that can be a good reference for a healthy diet! 

Other lifestyle advice that you can adopt include giving up smoking, cutting back on alcohol consumption, losing weight and frequent health examinations with your healthcare professionals!

This article is written by Rosamund, Bpharm(Hons) (DOC2US), 
reviewed by Dr. Ahmad Haniffan, MBBS​ (DOC2US)​​​​​​

References:

1. Cohen, L. (2020). Chris Hemsworth discovers he has rare genetic makeup that significantly increases risk of Alzheimer's disease: "My biggest fear". CBS News. Retrieved from https://www.cbsnews.com/news/chris-hemsworth-rare-genetic-makeup-alzheimers-disease/ 

2. National Institute on Aging (NIH). (2019). Alzheimer's Disease Genetics Fact Sheet. Retrieved from https://www.nia.nih.gov/health/alzheimers-disease-genetics-fact-sheet 

3. Centers for Disease Control and Prevention (CDC). (2020). Alzheimer’s Disease and Related Dementias. Retrieved from https://www.cdc.gov/aging/aginginfo/alzheimers.htm 

4. National Institute on Aging (NIH). (2019). What Do We Know About Diet and Prevention of Alzheimer's Disease? Retrieved from https://www.nia.nih.gov/health/what-do-we-know-about-diet-and-prevention-alzheimers-disease 

5. NHS. (2021). Causes of Alzheimer's disease. Retrieved from https://www.nhs.uk/conditions/alzheimers-disease/causes/ 

6. Zhou, Zi, Wang, Ping, & Fang, Ya. (2018). Social Engagement and Its Change are Associated with Dementia Risk among Chinese Older Adults: A Longitudinal Study. Scientific Reports, 8(1), 1551–1557. https://doi.org/10.1038/s41598-017-17879-w

Written By

Rosamund, Bpharm(Hons)

Reviewed By

Doc2us Medical Board