Apolipoprotein E: Emerging Story in the Pathogenesis of Alzheimer's Disease

Abstract

Apolipoprotein E (apoE) is implicated in the pathogenesis of Alzheimer's disease. One of the three com mon apoE alleles, apoE4, behaves as an autosomal codominant trait in the majority of late-onset and sporadic Alzheimer's disease, with homozygosity for this allele virtually sufficient to cause disease by the age of 80. In contrast, the apoE2 and apoE3 alleles decrease the probability of disease and increase the age of onset, with the protective effect of apoE2 greater than apoE3. Thus, the inherited alleles of apoE determine, in part, the risk of developing Alzheimer's disease and determine the rate of disease progres sion. Isoform-specific interactions of apoE with other molecules are therefore critical in this disease. ApoE is found in populations of neurons, some of which contain abnormal neurofibrillary tangles assembled from the protein tau. In healthy neurons, tau helps assemble and stabilize microtubules, but in Alzheimer's disease, it forms paired helical filaments of the neurofibrillary tangle. ApoE3 avidly binds tau in vitro, whereas apoE4 does not. Isoform-specific interactions of apoE with tau and other microtubule-associated proteins could contribute to the mechanism of Alzheimer's disease. Uncovering the roles of apoE in the brain, both in health and in disease, will be an exciting area for neuroscience. The Neuroscientist 1:298- 306, 1995