Alzheimer’s disease is a progressive brain disorder that damages and eventually destroys brain cells, leading to memory loss, confusion, and other issues that interfere with daily life. One of the biggest risk factors for Alzheimer’s is having a family history of the disease. Research has found that mutations in certain genes, like the APP, PSEN1, and PSEN2 genes, can increase a person’s risk of developing Alzheimer’s. This has led to questions about whether the Alzheimer’s gene can skip generations in a family.
Can you get Alzheimer’s if it runs in your family?
Having a parent, sibling, or child with Alzheimer’s does increase your risk of developing the disease. According to the Alzheimer’s Association, if you have a first-degree relative with Alzheimer’s, your risk is 2-3 times higher than the general population. The exact risk depends on different factors like at what age your family members developed the disease. But having a family history of Alzheimer’s is considered a risk factor overall.
This increased risk is thought to be due to both genetic and environmental factors that can run in families. So yes, if you have a family history of Alzheimer’s, you are at increased risk of developing it yourself compared to someone with no family history of the disease.
How genetics impact Alzheimer’s risk
Researchers have found several genes that increase Alzheimer’s risk. The most well-known are:
- APP – This gene helps produce beta-amyloid, the main component of the plaques characteristic of Alzheimer’s.
- PSEN1 – This gene produces a protein that helps cut the amyloid precursor protein.
- PSEN2 – This gene also produces a protein involved in cutting the amyloid precursor protein.
Mutations in these genes can lead to an overproduction of beta-amyloid and accumulation of plaques in the brain. Carrying one of these genetic mutations greatly increases your Alzheimer’s risk. However, these mutations are rare and account for less than 5% of Alzheimer’s cases.
More common is the APOE e4 gene. Having one copy of this gene variant doubles your risk while having two copies increases your risk up to 12 times higher. The APOE e4 gene impacts cholesterol levels and is thought to affect the clearance of beta-amyloid from the brain.
Can you inherit Alzheimer’s from a grandparent?
It is possible to inherit an increased genetic risk for Alzheimer’s disease from a grandparent. This is because of how certain mutations linked to Alzheimer’s are passed down.
For example, when a parent has a mutation in the APP, PSEN1 or PSEN2 gene, they have a 50/50 chance of passing that mutation down to their child. If the child inherits that mutation, they too are then at very high risk of developing Alzheimer’s. So in this scenario, it is possible for a grandparent’s Alzheimer’s gene to be passed to their grandchild, conferring increased risk.
More on inherited Alzheimer’s mutations
Here is some more information on how mutations linked to Alzheimer’s disease can be inherited:
- Autosomal dominant inheritance – Mutations in APP, PSEN1 and PSEN2 demonstrate an autosomal dominant pattern. This means you only need to inherit one copy of the mutation from a parent to develop the disease.
- 50% chance – Each child of an affected parent has a 50% chance of inheriting the mutation. If they inherit it, their risk for Alzheimer’s is very high.
- Can skip generations – Since there is a 50/50 chance of passing down the mutation in each pregnancy, it is possible for the mutation to skip generations if by chance a child doesn’t inherit it.
So in summary, yes certain Alzheimer’s mutations can be passed down from a grandparent. A grandchild’s risk depends on if their parent was a carrier of the mutation or not. Even if the disease seems to have “skipped” a generation in a family, the genetic risk can still be inherited.
What if you have the APOE e4 gene variant?
As mentioned earlier, the APOE e4 variant is the most common genetic risk factor for Alzheimer’s disease. Up to 25% of the population carries one copy of this gene. Unlike mutations in APP and PSEN genes, the APOE e4 variant does not cause Alzheimer’s by itself. Instead it increases risk, especially in people who carry two copies.
The inheritance pattern of APOE e4 is more complex than a simple dominant mutation. Here’s a quick breakdown:
- There are 3 forms of the APOE gene – e2, e3, and e4
- Everyone inherits two copies of APOE, one from each parent
- The e3 form is the most common, while e4 increases Alzheimer’s risk
- The risk depends on which combinations you inherit – e2/e4 has lower risk than e4/e4 for example
Because each child inherits a different combination from their parents, the inheritance of APOE e4 is not as straightforward. But there is still an increased chance of inheriting the e4 variant if a parent has it. So again, the Alzheimer’s risk gene can be passed down from grandparents in this scenario.
APOE e4 inheritance patterns:
| Parent 1 genes | Parent 2 genes | Child genotype | Risk |
|---|---|---|---|
| e3/e3 | e3/e4 | e3/e4 | Higher |
| e3/e4 | e3/e3 | e3/e4 or e3/e3 | Higher or Average |
| e4/e4 | e3/e4 | e4/e4 or e3/e4 | Highest or Higher |
Can Alzheimer’s skip a generation?
Based on the inheritance patterns discussed, it is possible for the Alzheimer’s gene to skip a generation in a family. This could happen in a few scenarios:
- A mutation is not passed down – If a parent has an Alzheimer’s mutation but does not pass it to their child, it appears to skip that generation.
- Onset age impacts perception – If early-onset Alzheimer’s occurs in a grandparent but a parent doesn’t live long enough to show symptoms, it may seem like it skipped the parent’s generation.
- APOE e4 is not inherited – Since APOE e4 inheritance is probabilistic, a parent may have the variant while the child does not, making it appear to skip.
However, experts warn that you cannot definitively say that Alzheimer’s skipped a generation based on observation alone. Just because a parent did not show symptoms of Alzheimer’s, does not mean they were not a carrier of a risk gene. The only way to know if a mutation or APOE e4 was passed down is through genetic testing.
Key points
- It is possible for mutations linked to early-onset Alzheimer’s, like those in the APP and PSEN genes, to skip a generation if the mutation is not inherited.
- Similarly, a parent may have the APOE e4 variant but not pass it to their child, so it appears to skip.
- Without genetic testing, you cannot confirm that the disease skipped a generation based on observation alone.
- Anyone with a family history of Alzheimer’s has an increased risk themselves and should be monitored for symptoms.
Does having an affected grandparent increase your risk?
Yes, having a grandparent with Alzheimer’s disease does increase your risk of developing it compared to the general population. However, your exact risk varies depending on if a parent was affected and which genetic factors are involved. Here’s a quick overview:
- Parent also affected – Your risk is highest if one of your parents also had Alzheimer’s. This could indicate an autosomal dominant inheritance of a genetic mutation.
- Parent unaffected – If your parent did not have Alzheimer’s but a grandparent did, your risk is lower but still increased compared to no family history.
- Onset age – If your grandparent had early-onset Alzheimer’s, your risk is higher than if they only developed it later in life.
- Number of relatives – The more relatives you have with Alzheimer’s, the higher your genetic risk is likely to be.
While having an affected grandparent does increase your risk, it does not guarantee you will develop Alzheimer’s disease. Environment, lifestyle, and other genetics come into play. But it does mean you should be monitored more closely by your doctor.
Steps to take if you have a family history
If you have a grandparent or other close relative with Alzheimer’s, here are some recommendations:
- Let your doctor know about any family history of dementia.
- Consider genetic testing if it’s recommended.
- Adopt healthy lifestyle habits, like exercise and a Mediterranean diet.
- Stay socially and mentally active.
- Report any cognitive changes you notice to your doctor.
- Discuss risk reduction strategies and research trials with your provider.
Being aware of your family history and any associated risks allows you to take proactive steps for early detection and prevention.
Could it be another type of dementia?
It’s also possible that a diagnosis of Alzheimer’s disease in older relatives may have actually been another type of dementia. The boundaries between different dementia diagnoses used to be less defined. Some other possibilities include:
Vascular dementia
Vascular dementia occurs due to damage to blood vessels in the brain. It can cause symptoms similar to Alzheimer’s like memory loss and confusion. There is often a history of stroke or heart disease in the family.
Lewy body dementia
This type of dementia involves abnormal deposits of the protein alpha-synuclein in the brain. Early symptoms can include sleep disturbances, well before memory loss. Lewy body dementia has some genetic links.
Frontotemporal dementia
In frontotemporal dementia, damage is focused on the frontal and temporal lobes of the brain. Personality and behavior changes tend to occur first. There are strong genetic factors in some families.
Since knowledge of dementia subtypes has advanced, it’s possible an alternative diagnosis better fits your family history. Genetic testing and brain imaging can help clarify the correct diagnosis today.
Conclusion
In summary, it is certainly possible for Alzheimer’s disease to appear to skip a generation in a family if by chance a mutation or risk gene is not passed down. However, anyone with a first-degree relative with Alzheimer’s has an increased risk themselves. Having multiple affected relatives across generations further raises that risk. While genes play a role, it is not a guarantee you will develop Alzheimer’s if a grandparent had it. Being aware of your family history allows you to be proactive and make lifestyle changes that may help reduce your risk. Consult your doctor about an appropriate prevention and monitoring plan.