According to new research, having two copies of the APOE4 gene variant may increase the risk of getting Alzheimer’s. The study also discovered that individuals with two copies of APOE4 are more likely to develop the disease earlier in life.
A recent study reveals that some Alzheimer’s cases have a direct hereditary origin [1].
No underlying cause for the majority of Alzheimer’s patients is currently known. Nonetheless, researchers have long understood that having an APOE4 gene variant in your family can increase your risk of being diagnosed. Individuals with two copies, which account for 2–5% of the population overall, are significantly more vulnerable [2].
Researchers have now proposed that possessing two copies of APOE4 may actually cause the condition rather than just increasing the likelihood of developing it.
A New Genetic Disorder
Researchers previously recognized two types of Alzheimer’s disease: familial and sporadic. The familial form results from genetic mutations, as the name implies. Typically, familial types are less common and develop early. Previously, medical practitioners believed less than 5% of cases, or around one in every fifty, were familial [3].
The new study suggests that 1 in 6 cases of Alzheimer’s would be due to the genetic type of the disease. This change occurred because scientists think they now have a better understanding of the role the APOE gene has in Alzheimer’s development. They believe they have discovered that a familial form of Alzheimer’s may be a separate disease rather than an offshoot.
Various forms of APOE that a person can have are:
- APOE2 protects against developing Alzheimer’s.
- APOE3 is considered neutral.
- APOE4 raises the risk of developing Alzheimer’s. Individuals who carry two copies of this gene are at a higher risk.
APOE4 was initially considered to be a risk factor. Scientists now believe that it is an inherited type of Alzheimer’s and a separate disease.
Details About the New Study
Researchers in the United States and Spain contrasted individuals with two copies of APOE4 to those with other forms of the APOE gene [1].
The researchers examined data from 10,000 participants in five clinical trials and data from about 3,297 brains kept at the National Alzheimer’s Coordinating Center. Examining the brains kept at the Coordinating Center, scientists discovered that 273 had two gene copies. About 240 of them had dementia.
Additionally, the researchers discovered that the condition manifested roughly ten years sooner in those with the APOE4 variant with an average onset age of 65. According to their results, those with this inherited form of Alzheimer’s developed the disease at a faster rate than those with other kinds of Alzheimer’s.
The researchers stated that possessing one copy of the gene raises the Alzheimer’s risk. However, having two copies increased the likelihood of developing beta-amyloid and tau buildup in the brain.
These findings led the researchers to hypothesize that individuals who have two copies of APOE4 have a genetic type of Alzheimer’s.
According to a previous study, approximately 30% to 35% of individuals with two copies of the APOE4 gene would get dementia or at least mild cognitive impairment [4].
However, APOE4 has a substantial association with cardiac disease. It is possible that individuals with two gene copies passed away from heart disease rather than dementia since they had died before the researchers started looking for dementia.
Researchers in the current study estimate that 15% of patients with Alzheimer’s disease carry two copies of APOE4. The APOE4 gene is present in two copies in about 2% of the general population, making it one of the most common hereditary disorders.
Future Implications of the Research
The new research highlights whether asymptomatic individuals should undergo genetic testing to know if they carry two copies of APOE4.
Most people who carry two APOE4 genes are those whose parents were both diagnosed with Alzheimer’s disease quite early on—probably in their 60s.
Genetic tests are not currently performed in clinical settings to diagnose or predict Alzheimer’s risk. Many specialists do not recommend it due to the complexity associated with analyzing the results.
According to the study’s authors, this type of testing could be beneficial, and doctors should recommend it to their patients.
Lecanemab is a drug used to treat Alzheimer’s disease by removing amyloid plaques from the brain. Knowing if an individual has two copies could be life-saving. However, people with two copies of APOE4 are more likely to have brain swelling from these medications and since this medicine can cause brain swelling, several treatment centers do not offer it.
June is Alzheimer’s and Brain Awareness Month. It aims to increase public awareness and motivate individuals to donate money or their time to support and research. Besides raising awareness about Alzheimer’s, it aims to provide opportunities to raise funds for research and support services for Alzheimer’s patients and their families. Donate to the Alzheimer’s Research Foundation to help us support the Alzheimer’s family caregivers and provide them with resources.
Donate now: https://www.alzra.org/donate-now/
References
- Fortea, J., Pegueroles, J., Alcolea, D., Belbin, O., Dols-Icardo, O., Vaqué-Alcázar, L., Videla, L., Gispert, J.D., Suárez-Calvet, M., Johnson, S.C. and Sperling, R., 2024. APOE4 homozygozity represents a distinct genetic form of Alzheimer’s disease. Nature Medicine, pp.1-8.
- Alzheimer’s Disease Genetics Fact Sheet. National Institute on Aging. https://www.nia.nih.gov/health/alzheimers-causes-and-risk-factors/alzheimers-disease-genetics-fact-sheet. Accessed: 7th June, 2024.
- Familial Alzheimer’s Disease. UCSF Weill Institute for Neurosciences. https://memory.ucsf.edu/genetics/familial-alzheimer-disease. Accessed: 7th June. 2024.
- Qian, J., Wolters, F.J., Beiser, A., Haan, M., Ikram, M.A., Karlawish, J., Langbaum, J.B., Neuhaus, J.M., Reiman, E.M., Roberts, J.S. and Seshadri, S., 2017. APOE-related risk of mild cognitive impairment and dementia for prevention trials: an analysis of four cohorts. PLoS medicine, 14(3), p.e1002254.
- Alzheimer’s disease may be inherited more often than previously thought. Medical News Today. https://www.medicalnewstoday.com/articles/alzheimers-disease-may-be-inherited-more-often-than-previously-thought. Published Online: 7th May, 2024. Accessed: 7th June, 2024.
- Study Identifies Genetic Variant as a Clear Cause of Alzheimer’s—Does This Mean You Should Get Tested? Health. https://www.health.com/genetics-causes-alzheimer-study-8648326. Published Online: 5th June, 2024. Accessed: 7th June, 2024.
