APOLIPOPROTEIN-E AND ALZHEIMERS-DISEASE - A REVIEW OF RECENT STUDIES

There are three isoforms of the 33-kDa protein apolipoprotein E (apoE) , termed apoE2, apoE3 and apoE4, each encoded by distinct genes APOE2, APOE3, and APOE4, respectively. In 1993, the APOE genotype was identi fied as a risk factor for Alzheimer's disease (AD) and was subsequentl y acknowledged to account for approximately 60% of all cases. The infl uence of the APOE genotype in AD is clearly isoform dependent, APOE4 i mparting susceptibility and APOE2 protection. Thus, patients homozygou s for the E4 allele show a very strong likelihood of developing the di sease by age 75, whereas patients carrying at least one E2 allele are unlikely to develop symptoms of AD by this age. A major issue in AD re search is therefore to understand the functional differences between t he ApoE isoforms, with the ultimate aim of designing the next generati on of drugs to treat this disease. The purpose of the present article is to summarise some of this work. This review encompasses the rapidly developing molecular, cellular, and behavioural research into ApoE, a nd attempts to highlight those findings we consider to be of particula r significance. (C) 1997 Elsevier Science Inc.