What is Alzheimer's disease and how does genetics (APOE) play a role?
Alzheimer's disease is the most common form of dementia, responsible for between 60% and 80% of cases. It is considered a neurocognitive condition linked to aging, as its frequency increases markedly with age. In Western populations, it affects approximately 1% of people aged 65, but impacts as many as one in four among those over 90. As the world's population ages, millions of people are facing, directly or indirectly, this diagnosis that impairs memory, reasoning, orientation and, over time, even the ability to perform basic day-to-day tasks.
Although Alzheimer's disease is a complex disease influenced by multiple factors, one of the most important is most studied genetic elements is the gene APOE. This gene has several common variants that can increase or decrease the risk of developing it. In particular, the people that inherit two copies of the variant APOE-ε4 have a risk of between 8 and 10 times greater of suffering from Alzheimer's compared to those who do not have it.
What is lecanemab and why is it important to know the genetic profile (APOE)?
The revolutionary drug lecanemab focuses on slowing cognitive decline in the early stages of Alzheimer's disease. This is a monoclonal antibody marketed as Leqembi. Its mission is to directly attack one of the causes of Alzheimer's disease: the accumulation of a protein called beta-amyloid in the brain. When this protein aggregates, it forms neuritic plaques associated with neuronal death and loss of cognitive function. Lecanemab binds to these aggregates and signals for the immune system to recognize and eliminate them.This helps to reduce the accumulation of beta-amyloid in the brain.
This drug has been approved by the European Commission (EC) on April 15th, 2025 to treat mild cognitive impairment in the early stages of Alzheimer's disease in the European Union. With the aim of reducing the drug's side effects, the drug has been approved for patients only with beta-amyloid plaques in the brain that only have one copy or none of ApoE4.
According to EMA, "patients with only one copy or no copies of ApoE4 are less likely to experience amyloid-related imaging abnormalities (ARIA) that individuals with two copies of ApoE4. The ARIA is a serious side effect recognized with Leqembi involving swelling and possible hemorrhage in the brain."
In addition to the strict conditions imposed by the European Commission, for the same reason the U.S. Food and Drug Administration (FDA), which approved the use of this drug in the US a year ago, recommends genetic testing for this variant before starting treatment.
How can I know my APOE genetic profile?
The gene configuration APOE is determined by the combination of two genetic variants. Thanks to advances in genetics, it is now possible to know this information quickly, easily and affordably using different technologies. Companies such as ADNTRO offer accessible genetic tests that can identify whether a person carries variants such as APOE-ε4The results of this study are key to assessing the risk of Alzheimer's disease and the suitability of treatments such as lecanemab.
What does the evidence say about the effect of Lecanemab?
The most important clinical trial backing lecanemab is called CLARITY, a Phase 3 study with 1,800 participants affected by mild cognitive impairment or in the mild stage of dementia as a result of Alzheimer's disease
In that trial, patients were treated with lecanemab for 18 months and observed that the drug slowed cognitive decline by 27% compared to those who received placebo.
As with any drug, lecanemab may present side effects such as dizziness, headache, vision changes, worsening confusion, brain swelling or bleeding, and brain shrinkage. For that reason, the European Commission has restricted the use of this drug to patients with none or one copy of the APOE-ε4 configuration. Excluding patients at increased risk of developing serious adverse effects.
