Genes known to increase the risk of Alzheimer’s may actually be an inherited form of the disorder, researchers say | CNN

🌈 Abstract

The article discusses a new study that suggests Alzheimer's disease may be inherited more often than previously thought. The study found that having two copies of the APOE4 gene should be considered a distinct, inherited form of Alzheimer's disease, rather than just a risk factor. This means that a much larger proportion of Alzheimer's cases are caused by genetics than previously understood.

🙋 Q&A

[01] Inherited Forms of Alzheimer's Disease

1. What are the key findings of the study regarding the role of the APOE4 gene in Alzheimer's disease?

• The study found that having two copies of the APOE4 gene is associated with:
  • A near-certainty (95%) of developing the biological changes linked to Alzheimer's disease by age 82
  • Developing Alzheimer's symptoms about 10 years earlier, around age 65, on average
  • A disease progression and symptom profile similar to other inherited forms of Alzheimer's

2. How does this change the understanding of the genetic contribution to Alzheimer's disease?

• Prior to this study, only about 2% of Alzheimer's cases were thought to be caused by inherited genetic factors.
• The new findings suggest that people with two copies of the APOE4 gene make up about 15% of Alzheimer's cases, or 1 in 7 cases.
• This means a much larger proportion of Alzheimer's cases are caused by genetics than previously understood.

3. What are the implications of classifying APOE4 as an inherited form of Alzheimer's disease?

• It suggests the need for personalized approaches to testing and treatment for Alzheimer's patients based on their genetic profile.
• It may lead to changes in guidelines around APOE4 genetic testing, which is currently not recommended routinely.
• It highlights the importance of considering APOE4 status in clinical trials of Alzheimer's treatments.

[02] Implications for Diagnosis and Treatment

1. How does the APOE4 gene status impact the use of amyloid-clearing medications?

• Patients with two copies of the APOE4 gene are at higher risk of serious side effects like brain swelling from amyloid-clearing medications.
• Some treatment centers have decided not to offer these medications to APOE4 homozygous patients, which the study authors find problematic.
• The researchers suggest the need to find safer dosing or treatments for this patient group, and to consider treating them earlier in the disease process.

2. What is the importance of considering APOE4 status in Alzheimer's research and clinical trials?

• The study authors argue that clinical trials should start taking participants' APOE4 status into account.
• This would allow researchers to better understand the relationship between amyloid, tau, and symptoms in APOE4 homozygous individuals, which has been difficult to do previously.