Journal of Neural Transmission

, Volume 126, Issue 1, pp 65–85 | Cite as

Clinical implications of APOE genotyping for late-onset Alzheimer’s disease (LOAD) risk estimation: a review of the literature

  • Victoria S. Marshe
  • Ilona Gorbovskaya
  • Sarah Kanji
  • Maxine Kish
  • Daniel J. MüllerEmail author
Psychiatry and Preclinical Psychiatric Studies - Review Article


Alzheimer’s disease is a genetically complex neurodegenerative disorder representing the leading cause of dementia. Advances in personal genomics are increasing the public uptake of genetic susceptibility testing for complex diseases such as late-onset Alzheimer’s disease (LOAD). For LOAD, the discovery of the major risk ε4 allele of the APOE gene has prompted a debate on the ethics and utility of presymptomatic (i.e., predictive) testing. Although the mechanistic contribution of APOE to disease onset remains uncertain, presymptomatic genetic testing provides a relative risk of developing LOAD. Presymptomatic testing for complex disorders, such as LOAD is much less conclusive than early-onset Alzheimer’s disease (EOAD) which follows a Mendelian inheritance pattern. Given the lack of preventive strategies available for EOAD or LOAD, APOE genotyping offers limited clinical utility, thus, raising ethical and practical questions. We conducted a systematic search of five electronic databases or primary studies published during January 2008–January 2018 which investigated practical and ethical issues of presymptomatic APOE genotyping for LOAD risk estimation. We identified 31 articles which suggested that APOE genotyping for LOAD susceptibility provides potential benefits to at-risk patients and can guide changes in positive health-related behaviors. However, other individuals may experience test-related anxiety, depression and psychological distress. Future research should focus on developing an integrated risk assessment tool to enhance the utility of APOE genotyping. Furthermore, empirical research is required to understand actual psychological and social implications associated with testing.


Genetic testing Direct-to-consumer APOE Alzheimer’s disease Ethics 


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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  • Victoria S. Marshe
    • 1
    • 2
  • Ilona Gorbovskaya
    • 2
  • Sarah Kanji
    • 2
    • 3
  • Maxine Kish
    • 2
    • 4
  • Daniel J. Müller
    • 1
    • 2
    • 5
    Email author
  1. 1.Institute of Medical ScienceUniversity of TorontoTorontoCanada
  2. 2.Pharmacogenetics Research Clinic, Campbell Family Mental Health Research InstituteCentre for Addiction and Mental HealthTorontoCanada
  3. 3.Faculty of MedicineUniversity of TorontoTorontoCanada
  4. 4.Faculty of MedicineQueen’s UniversityKingstonCanada
  5. 5.Department of PsychiatryUniversity of TorontoTorontoCanada

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