Pharmacogenetics or predictive genetics? APOE testing blurs the lines
The integration of pharmacogenetics into personalized medicine enables the optimization of drug selection and dosage, maximizing therapeutic benefits while minimizing the risk of adverse drug reactions. The association between APOE alleles and ARIA, a known adverse reaction in Alzheimer’s disease pa...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-07-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1627239/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849429822906826752 |
|---|---|
| author | Stefania Zampatti Cristina Peconi Juliette Farro Fabrizio Piras Clelia Pellicano Carlo Caltagirone Emiliano Giardina Emiliano Giardina |
| author_facet | Stefania Zampatti Cristina Peconi Juliette Farro Fabrizio Piras Clelia Pellicano Carlo Caltagirone Emiliano Giardina Emiliano Giardina |
| author_sort | Stefania Zampatti |
| collection | DOAJ |
| description | The integration of pharmacogenetics into personalized medicine enables the optimization of drug selection and dosage, maximizing therapeutic benefits while minimizing the risk of adverse drug reactions. The association between APOE alleles and ARIA, a known adverse reaction in Alzheimer’s disease patients treated with anti-amyloid monoclonal antibodies, has led to the inclusion of APOE genotyping among conventional pharmacogenetic tests. Given the dual role of APOE alleles, the widespread implementation of this genetic test requires caution and should be accompanied by appropriate genetic counselling. APOE genotyping is uniquely positioned at the intersection of pharmacogenetics and germline testing: it provides insight not only into drug safety (specifically the risk of Amyloid-Related Imaging Abnormalities) but also into familial risk for developing Alzheimer’s disease. Carriers of risk alleles, especially homozygotes, face the highest risk and require close monitoring. While APOE genotyping can inform treatment decisions, it also raises ethical concerns due to the broader implications of disclosing genetic risk information for neurodegenerative diseases. Identifying a high-risk APOE genotype in a patient substantially impacts family members. Therefore, patients considered for treatment with anti-amyloid monoclonal antibodies should receive comprehensive pre- and post-test genetic counseling that goes beyond traditional standards, as currently provided for other peculiar tests. Such counseling ensures that patients are adequately informed about potential outcomes, psychological impacts, and familial implications. It also supports ethical decision-making and facilitates truly informed consent, helping to prevent deterministic or overly simplistic interpretations of genetic risk. |
| format | Article |
| id | doaj-art-d3f242b07f2a471a939a3c747ea6e054 |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-d3f242b07f2a471a939a3c747ea6e0542025-08-20T03:28:13ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-07-011610.3389/fphar.2025.16272391627239Pharmacogenetics or predictive genetics? APOE testing blurs the linesStefania Zampatti0Cristina Peconi1Juliette Farro2Fabrizio Piras3Clelia Pellicano4Carlo Caltagirone5Emiliano Giardina6Emiliano Giardina7Genomic Medicine Laboratory UILDM, IRCCS Santa Lucia Foundation, Rome, ItalyGenomic Medicine Laboratory UILDM, IRCCS Santa Lucia Foundation, Rome, ItalyGenomic Medicine Laboratory UILDM, IRCCS Santa Lucia Foundation, Rome, ItalyNeuropsychiatry Laboratory, Department of Clinical Neuroscience and Neurorehabilitation, IRCCS Santa Lucia Foundation, Rome, ItalyNeuropsychiatry Laboratory, Department of Clinical Neuroscience and Neurorehabilitation, IRCCS Santa Lucia Foundation, Rome, ItalyDepartment of Clinical and Behavioral Neurology, IRCCS Fondazione Santa Lucia, Rome, ItalyGenomic Medicine Laboratory UILDM, IRCCS Santa Lucia Foundation, Rome, ItalyDepartment of Biomedicine and Prevention, Tor Vergata University, Rome, ItalyThe integration of pharmacogenetics into personalized medicine enables the optimization of drug selection and dosage, maximizing therapeutic benefits while minimizing the risk of adverse drug reactions. The association between APOE alleles and ARIA, a known adverse reaction in Alzheimer’s disease patients treated with anti-amyloid monoclonal antibodies, has led to the inclusion of APOE genotyping among conventional pharmacogenetic tests. Given the dual role of APOE alleles, the widespread implementation of this genetic test requires caution and should be accompanied by appropriate genetic counselling. APOE genotyping is uniquely positioned at the intersection of pharmacogenetics and germline testing: it provides insight not only into drug safety (specifically the risk of Amyloid-Related Imaging Abnormalities) but also into familial risk for developing Alzheimer’s disease. Carriers of risk alleles, especially homozygotes, face the highest risk and require close monitoring. While APOE genotyping can inform treatment decisions, it also raises ethical concerns due to the broader implications of disclosing genetic risk information for neurodegenerative diseases. Identifying a high-risk APOE genotype in a patient substantially impacts family members. Therefore, patients considered for treatment with anti-amyloid monoclonal antibodies should receive comprehensive pre- and post-test genetic counseling that goes beyond traditional standards, as currently provided for other peculiar tests. Such counseling ensures that patients are adequately informed about potential outcomes, psychological impacts, and familial implications. It also supports ethical decision-making and facilitates truly informed consent, helping to prevent deterministic or overly simplistic interpretations of genetic risk.https://www.frontiersin.org/articles/10.3389/fphar.2025.1627239/fullpharmacogeneticspredictive testgenetic counsellingalzheimer diseasemonoclonal antibodiesAPOE |
| spellingShingle | Stefania Zampatti Cristina Peconi Juliette Farro Fabrizio Piras Clelia Pellicano Carlo Caltagirone Emiliano Giardina Emiliano Giardina Pharmacogenetics or predictive genetics? APOE testing blurs the lines Frontiers in Pharmacology pharmacogenetics predictive test genetic counselling alzheimer disease monoclonal antibodies APOE |
| title | Pharmacogenetics or predictive genetics? APOE testing blurs the lines |
| title_full | Pharmacogenetics or predictive genetics? APOE testing blurs the lines |
| title_fullStr | Pharmacogenetics or predictive genetics? APOE testing blurs the lines |
| title_full_unstemmed | Pharmacogenetics or predictive genetics? APOE testing blurs the lines |
| title_short | Pharmacogenetics or predictive genetics? APOE testing blurs the lines |
| title_sort | pharmacogenetics or predictive genetics apoe testing blurs the lines |
| topic | pharmacogenetics predictive test genetic counselling alzheimer disease monoclonal antibodies APOE |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1627239/full |
| work_keys_str_mv | AT stefaniazampatti pharmacogeneticsorpredictivegeneticsapoetestingblursthelines AT cristinapeconi pharmacogeneticsorpredictivegeneticsapoetestingblursthelines AT juliettefarro pharmacogeneticsorpredictivegeneticsapoetestingblursthelines AT fabriziopiras pharmacogeneticsorpredictivegeneticsapoetestingblursthelines AT cleliapellicano pharmacogeneticsorpredictivegeneticsapoetestingblursthelines AT carlocaltagirone pharmacogeneticsorpredictivegeneticsapoetestingblursthelines AT emilianogiardina pharmacogeneticsorpredictivegeneticsapoetestingblursthelines AT emilianogiardina pharmacogeneticsorpredictivegeneticsapoetestingblursthelines |