If Someone in the Family Has Alzheimer's Disease, Are the Next Generations Doomed to Get It?

Alzheimer's disease has become increasingly common in recent years. According to statistics, by 2020, the total population of older adults aged 60 and above in China had reached 260 million [1], among whom 38.87 million had mild cognitive impairment and 9.83 million had Alzheimer's disease.

This leads many people to worry: if someone in the family has this condition, does it mean I'm more likely to develop it too?

I. Alzheimer's Disease: Don't Mistake the Disease for Aging!

Many people mistakenly believe that Alzheimer's disease is simply "becoming senile," "getting forgetful," "becoming less capable"—a normal part of aging. Reports show that 85% of affected families attribute memory decline in their elderly relatives to the natural aging process, seeing no need for treatment, leading to delays in seeking medical help. Nearly 60% of patients only visit a doctor after symptoms appear, while only 10% of patients receive a clear diagnosis after cognitive issues are identified during routine checkups.

In reality, Alzheimer's disease is a serious neurodegenerative condition. Memory loss is only the first step; patients ultimately develop severe short-term and long-term memory impairment, which then affects thinking, language, and behavior, eventually leading to loss of independence.

Therefore, we must stop viewing Alzheimer's symptoms as an inevitable part of aging! What we need to do is understand the disease correctly, recognize it early, and seek medical attention promptly when necessary.

II. Is Alzheimer's Disease Hereditary? Risks Differ by Type

Returning to the most pressing question: Is Alzheimer's disease hereditary? The answer is—yes, but it depends on the specific type.

Clinically, Alzheimer's disease is primarily divided into early-onset and late-onset types. Early-onset Alzheimer's disease is relatively rare, with onset typically occurring before age 65, accounting for less than 5% of cases. Late-onset Alzheimer's is more common, with onset after age 65, accounting for over 95% of cases. These two types have distinct genetic characteristics.

1. Early-Onset Alzheimer's Disease

This form is associated with mutations in genes such as amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2). [2] These are causal genes—mutations in them directly lead to the development of Alzheimer's. This means that if one parent has early-onset Alzheimer's, the probability of their children inheriting the causative gene is as high as 50%. If the causative gene is inherited, the likelihood of developing the disease at a specific age is very high.

In the film Still Alice, the protagonist develops the disease around age 50 due to a family genetic mutation, gradually losing her memory and ability to care for herself.

2. Late-Onset Alzheimer's Disease

In contrast, the genetic mechanism of late-onset Alzheimer's is more complex. It is not determined by a single gene mutation but rather results from the interaction of multiple genes and environmental factors.

Among the relevant genes, the APOE gene has the strongest association with disease risk. The APOE gene is an important gene in our body, encoding a protein that plays a key role in the brain, such as transporting lipids like cholesterol. There are three different alleles of the APOE gene: APOE ε2, APOE ε3, and APOE ε4.

When the APOE gene undergoes a variation resulting in the APOE ε4 type, it affects the degradation and deposition of amyloid-beta in the brain, leading to an increased risk of developing Alzheimer's disease.

It is worth noting that while APOE ε4 was previously considered a risk gene, a recent study has redefined its relationship with Alzheimer's.

3. Major Finding: APOE ε4—From Risk to Cause

In 2024, a study published in Nature Medicine proposed that APOE ε4 should no longer be considered merely a risk gene for Alzheimer's disease, but should be recognized as a causative gene. [2]

Researchers analyzed brain pathology data from nearly 3,300 donors in the National Alzheimer's Coordinating Center (NACC) cohort, along with clinical data from over 10,000 individuals across five large multi-center cohorts. Their findings revealed:

· Compared to APOE ε3 homozygotes, nearly all APOE ε4 homozygotes (individuals carrying two copies of the APOE ε4 gene) showed higher levels of Alzheimer's biomarkers as early as age 55.

· APOE ε4 homozygotes began showing symptoms at approximately 65.6 years of age, developed mild cognitive impairment at 71.8 years, progressed to dementia at 73.6 years, and passed away at 77.2 years—approximately 7 to 10 years earlier than APOE ε3 homozygotes.

We have long known that the APOE ε4 gene is a significant risk factor for Alzheimer's disease. This latest research confirms a direct causal link between the APOE ε4 gene and Alzheimer's. This provides a new framework for Alzheimer's prevention: individuals carrying two copies of the APOE ε4 gene should pay closer attention to their health status and undergo regular physical examinations and cognitive assessments.

III. APOE Genetic Testing: A Tool for Early Risk Detection

How can you know if you or a family member carries the APOE ε4 gene? Genetic testing can unlock this mystery!

For at-risk individuals, undergoing APOE genetic testing early can help reveal the risk of developing Alzheimer's. If high-risk factors such as carrying two copies of the APOE ε4 gene are identified, preventive measures are recommended to delay or reduce the likelihood of developing Alzheimer's disease.

[1] Longfei Jia MD, Prof Yifeng Du MD, Prof Lan Chu MD, et al. Prevalence, risk factors, and management of dementia and mild cognitive impairment in adults aged 60 years or older in China: a cross-sectional study. The Lancet Public Health. Volume 5, Issue 12, December 2020, Pages e661-e671. Volume 5, Issue 12, December 2020, Pages e661-e671
https://www.sciencedirect.com/science/article/pii/S2468266720301857

[2] Juan Fortea, Jordi Pegueroles, Daniel Alcolea, et al. APOE4 homozygosity represents a distinct genetic form of Alzheimer’s disease. Nature Medicine. 30, pages1284–1291 (2024).
https://www.nature.com/articles/s41591-024-02931-w