ApoE and Alzheimer's Disease -- 10 Years Later

Highlights of the 9th International Conference on Alzheimer's Disease and Related Disorders; July 17-22, 2004; Philadelphia, Pennsylvania

Sara M. Mariani, MD, PhD

Disclosures
In This Article

Introduction

What have all these years of research contributed to our understanding of the role of apolipoprotein E (apoE) polymorphisms in Alzheimer's disease (AD)?[1,2,3]

The risk of developing AD at an earlier age than average is, in fact, correlated with the APOE allele carried by an individual, with the risk associated with APOE4 > E3 > E2. In a recent study, the mean age at AD onset was 68 years in patients with 2 E4 alleles, 75 years with 1 E4 allele, and 84 years in individuals with no E4 alleles. The importance of these associations is underscored by the fact that APOE4 was found linked to about 50% of AD cases analyzed.[1,2]

When the results are analyzed in terms of relative risk, as done by Farrer and colleagues,[4] the APOE4 allele was found associated with an increased risk of AD, whereas the E2 allele appeared to have a protective effect. The relative risk of AD for individuals E4/E4 was in fact 14.9; for E3/E4, 3.2; for E2/E4, 2.6; and for E2/2, .6.

Beyond genetic analysis, more data on the structure/functions of apoE proteins and their mechanisms of action that may explain their association with AD have recently become available, and were discussed at the 9th International Conference on Alzheimer's Disease and Related Disorders by leading investigators. We report here on 2 such presentations that give an idea as to how widely researchers are casting their nets to understand the biological function of apoE and its putative role in the development of minimal cognitive impairment (MCI) and AD. Data are being accumulated and novel hypotheses put forward.

If indeed apoE substantially contributes to MCI and AD, and 1-2 of its isoforms have a protective/therapeutic effect, then new roads for intervention in AD patients may open up in the future.

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