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

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 epsilon 4 of apolipoprotein E4 (APOE epsilon 4), 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 epsilon 4 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. (C) 2014 The Alzheimer's Association. All rights reserved.