A study has revealed that a specific gene (APOE4) that was known to increase the risk of Alzheimer’s disease is actually a direct cause. Individuals with this gene are almost certain to develop Alzheimer’s disease, so despite the risks of side effects, there is an argument for the need for drug treatment.
Researchers at the Barcelona Institute for Biomedical Research in Spain announced in the international journal ‘Nature Medicine’ on the 6th that over 95% of Alzheimer’s patients have a pair of mutations of the apolipoprotein E4 (APOE4) gene, which leads to the development of Alzheimer’s disease.
Alzheimer’s disease is a condition where abnormal amyloid beta protein accumulates in the brain, leading to a decline in cognitive function and memory. It typically occurs in individuals over the age of 65 and is also known as senile dementia.
The apolipoprotein E (APOE) protein is responsible for transporting cholesterol and lipids. However, when there is a mutation to the APOE4 form, the risk of developing Alzheimer’s disease significantly increases. Individuals with only one copy of APOE4 have about a 2.7 times higher risk of developing Alzheimer’s disease, while those with two copies have a risk that is about 17.4 times higher.
Based on research involving the observation of brain tissues from 3297 brain donors conducted for research purposes, it was found that all 273 individuals who had a pair of APOE4 genes had abnormal accumulation of amyloid beta protein in their brains. Furthermore, analysis of brain information from over 10,000 living individuals showed that those with two copies of the APOE4 gene had higher levels of amyloid beta protein in cerebrospinal fluid. This level increased with age, and among those with positive amyloid results, one out of two individuals is likely to develop Alzheimer’s disease within 3 years.
Researchers have concluded that APOE4 is a direct cause of Alzheimer’s disease. It is predicted that individuals with two copies of APOE4 may start showing Alzheimer’s disease symptoms at an earlier age of around 65.1 years, which is 7-10 years earlier than others.
The challenge lies in the fact that individuals with APOE4 are known to experience side effects with Lequembi, touted as the “dream dementia drug.” Developed by the US company Biogen and Japanese company Eisai, Lequemb provides cognitive decline by removing amyloid beta protein clumps from the brain. It was approved by the US Food and Drug Administration (FDA) in July last year. However, when individuals with APOE4 receive Lequemb, there is a 40% risk of brain hemorrhage or brain edema as the amyloid beta protein detaches from the blood vessel wall, causing damage.
Based on these research findings, researchers argue that patients with the APOE4 gene type should still use Lequemb. They emphasize that preventing Alzheimer’s disease is more crucial than the side effects. Reisa Sperling, a participant in this study and a professor of neurology at Brigham and Women’s Hospital, Harvard Medical School in the United States, stated to The Guardian, “People with this gene are prone to developing Alzheimer’s disease, so it is more proactive to undergo drug treatment” and added, “Preventive drug use before the onset of Alzheimer’s disease should also be researched.”
Reference:
Nature Medicine (2024) DOI: https://doi.org/10.1038/s41591-024-02931-w