APOE ε4: the most prevalent yet understudied risk factor for Alzheimer's disease

Alzheimers Dement. 2014 Nov;10(6):861-8. doi: 10.1016/j.jalz.2014.06.015. Epub 2014 Sep 10.


Brain pathology of Alzheimer's diseases (AD) and the genetics of autosomal dominant familial AD have been the "lamp posts" under which the AD field has been looking for therapeutic targets. Although this approach still remains valid, none of the compounds tested to date have produced clinically meaningful results. This calls for developing complementary therapeutic approaches and AD targets. The allele ε4 of apolipoprotein E4 (APOE ε4), is the most prevalent genetic risk factor for sporadic AD, and is expressed in more than half of the AD patients. However, in spite of its genetic prominence, the allele APOE ε4 and its corresponding protein product apoE4 have been understudied. We presently briefly discuss the reasons underlying this situation and review newly developed AD therapeutic approaches that target apoE4 and which pave the way for future studies.

Keywords: Alzheimer's disease; ApoE4; Immunotherapy; Lipidation; Therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / epidemiology*
  • Alzheimer Disease / genetics*
  • Apolipoprotein E4 / genetics*
  • Humans
  • Risk Factors


  • Apolipoprotein E4