Since July 2023, three anti-amyloid medications have been FDA-approved for the treatment of Alzheimer’s disease, with more medications in development. A potential side effect of these medications is amyloid-related imaging abnormalities (ARIA), which can lead to swelling or small bleeding areas in the brain. People carrying the apolipoprotein E-E4 gene (APOE-e4) are at a higher risk of developing ARIA when taking anti-amyloid drugs. Researchers have developed a new test to determine APOE variants a person may have to predict their reaction to these medications. The EURORealTime APOE test is a real-time PCR test that amplifies genomic DNA from blood to detect the three APOE alleles a person may have.
The first anti-amyloid medication approved by the FDA was lecanemab, sold as Leqembi, in July 2023, followed by donanemab (Kisunla) and more in development. ARIA is a serious side effect of anti-amyloid medications, involving brain swelling or small bleeding areas, particularly in individuals with the APOE-e4 gene. The EURORealTime APOE test developed by researchers at Revvity’s EUROIMMUN helps determine APOE variants to predict potential negative reactions to these medications. The test is currently available for research use only and aims to improve patient stratification for clinical trials and enhance personalized medicine for Alzheimer’s disease patients.
The APOE-e4 allele is associated with an increased risk of Alzheimer’s disease, with people carrying two copies of the allele having up to a 15 times higher risk. Individuals with the APOE-e4 gene are also more likely to experience ARIA as a side effect of anti-amyloid drugs, which can limit treatment effectiveness. ARIA can manifest as brain swelling (ARIA-E) or small bleeding events (ARIA-H) and may result in serious and potentially life-threatening events. The EURORealTime APOE test aims to identify individuals at higher risk of ARIA to help healthcare providers make informed treatment decisions.
Experts believe that being able to accurately genotype APOE alleles using the EURORealTime APOE test can improve risk stratification for patients receiving anti-amyloid medications for Alzheimer’s disease. The test offers a sensitive and reliable method for determining APOE variants, allowing for more precise treatment planning and potentially reducing the risk of serious side effects like ARIA. Further research is needed to validate the test’s accuracy across different populations and integrate it into routine clinical practice to enhance the safety and efficacy of Alzheimer’s disease therapies.
As the use of anti-amyloid medications increases in patients with mild cognitive impairment or mild dementia due to Alzheimer’s disease, identifying individuals at high risk of ARIA due to the APOE-e4 gene becomes crucial. The EURORealTime APOE test provides an opportunity for doctors to assess the risk of adverse reactions to anti-amyloid drugs before prescribing them, potentially preventing serious complications such as brain swelling and bleeding. For the test to be widely adopted, it needs to be accessible, cost-effective, and covered by insurance to ensure that patients receive the most appropriate and effective treatments based on their genetic profile. Further research and clinical studies are essential to understand the long-term implications of ARIA and to minimize its occurrence in patients with Alzheimer’s disease.
