From the Guidelines
Genetic testing for Alzheimer's disease should focus on mutations in the APP, PSEN1, and PSEN2 genes, which are linked to early-onset familial Alzheimer's disease, particularly in individuals with a strong family history of early-onset Alzheimer's (before age 65) 1. When considering genetic testing for Alzheimer's disease, it is essential to prioritize the most recent and highest quality studies. The 2025 study published in Alzheimer's and Dementia provides the most up-to-date guidance on genetic counseling and testing for Alzheimer's disease 1.
Key Considerations
- The most commonly tested mutations are in the APP, PSEN1, and PSEN2 genes, which are linked to early-onset familial Alzheimer's disease.
- Testing for these mutations is typically recommended when there is a strong family history of early-onset Alzheimer's (before age 65).
- Genetic testing should be accompanied by genetic counseling to help individuals understand the implications of results.
- A positive test does not guarantee disease development, and a negative test does not eliminate risk.
Additional Genes
Other genes that may be included in comprehensive panels include:
- TREM2
- SORL1
- ABCA7 However, the primary focus should remain on the APP, PSEN1, and PSEN2 genes, as they are the most strongly associated with early-onset familial Alzheimer's disease 1.
Importance of Genetic Counseling
Genetic counseling is a crucial component of genetic testing for Alzheimer's disease. It helps individuals understand the implications of their test results and makes informed decisions about their care. The counseling process should be conducted by an experienced genetic counselor and should include discussions about the potential risks and benefits of testing, as well as the implications of positive or negative results 1.
From the Research
Genetic Mutations for Alzheimer's Disease
The following genetic mutations can be tested for Alzheimer's disease:
- APP gene mutations 2, 3, 4, 5
- PSEN1 gene mutations 2, 3, 4, 6, 5
- PSEN2 gene mutations 2, 3, 4, 5
- APOE gene mutations, although APOE genotyping is not recommended for presymptomatic individuals with a family history of late-onset disease 2, 3
Testing Recommendations
Genetic testing for Alzheimer's disease is available for:
- Individuals with AD symptoms and at-risk children or siblings of patients with early-onset disease determined by a known mutation 2
- Patients with a positive family history of early-onset dementia and clinical features suggesting AD 3
- Familial cases of early-onset Alzheimer's disease 4
Limitations and Considerations
- Genetic testing should be performed under guidelines developed by relevant medical organizations 3
- Predictive testing should be performed with appropriate pretest and post-test counseling 3
- APOE genotyping should not be performed in asymptomatic individuals, except as part of an ethically approved research project 3
- Genetic risk factors other than APOE require validation and should not be used routinely, except as part of an ethically approved research protocol 3