Since July 2023, three anti-amyloid medications have been FDA-approved for the treatment of Alzheimer’s disease, with more in development. However, one potential and serious side effect of these medications is amyloid-related imaging abnormalities (ARIA), where swelling or small bleeding areas of the brain occur. People who carry the apolipoprotein E-E4 gene (APOE-e4) are at a higher risk of developing ARIA when taking these drugs. To address this issue, researchers at Revvity’s EUROIMMUN have developed a new test, called the EURORealTime APOE test, to help determine which APOE variants a person may have, potentially predicting whether or not they would have a negative reaction to anti-amyloid medications. The study was presented at the Association for Diagnostics & Laboratory Medicine (ADLM) 2024, but results are yet to be published in a peer-reviewed journal.
In July 2023, the U.S. Food and Drug Administration (FDA) approved lecanemab, sold under the brand name Leqembi, as the first anti-amyloid medication for the treatment of Alzheimer’s disease. Donanemab (Kisunla) has also received FDA approval, with more anti-amyloid medications still in development. ARIA, the potential side effect of these drugs, can manifest as either brain swelling (ARIA-E) or small bleeding events in the brain (ARIA-H), which can have serious and life-threatening consequences, including death. ARIA is more common and severe in individuals with the APOE-e4 allele, further emphasizing the importance of predicting and managing these side effects before initiating treatment with anti-amyloid drugs.
The EURORealTime APOE test is a real-time PCR test that amplifies genomic DNA isolated from whole blood to detect the three APOE alleles that a person may have in their genome. APOE-e4 allele carriers are at increased risk for developing Alzheimer’s disease and experiencing ARIA when treated with anti-amyloid drugs. While the test is currently available for research use only, further research and clinical studies are needed to better understand an individual’s risk of developing ARIA with these medications. APOE genotyping can also aid in patient stratification for clinical trials and personalized treatment approaches based on genetic profiles, ultimately improving outcomes for patients with Alzheimer’s disease.
Neurologists and experts in the field, including Verna Porter, MD, and Rehan Aziz, MD, have expressed cautious optimism about the EURORealTime APOE test’s potential to accurately genotype APOE in patients and predict the risk of severe side effects from anti-amyloid drugs. Dr. Porter notes that the test holds promise for improving risk stratification and tailoring treatments more precisely, enhancing the safety and efficacy of Alzheimer’s disease therapies. Dr. Aziz emphasizes the importance of identifying high-risk patients before prescribing anti-amyloid medications to prevent or reduce the risk of ARIA, which can lead to worsening symptoms, hospitalization, or even death. However, for widespread adoption, the test must be cost-effective, accessible, and covered by insurance.
Future research should focus on larger, diverse clinical trials to validate the EURORealTime APOE test’s accuracy and reliability across populations. Integrating genotyping tests like this into routine clinical practice and developing guidelines for their use in treatment planning will be essential. The goal is to minimize the risks associated with ARIA and enhance patient outcomes through personalized medicine approaches in Alzheimer’s disease treatment. Overall, advancements in precision medicine and genetic testing hold significant promise for improving the safety and effectiveness of anti-amyloid therapies, paving the way for a more targeted and customized approach to managing Alzheimer’s disease.
