Apolipoprotein E: A potent gene-based therapeutic target for the treatment of sporadic Alzheimer's disease

Abstract

Alzheimer's disease (AD) is associated with neuronal loss, synaptic damage, deposition of β-amyloid, and loss of cholinergic activity in susceptible brain regions. The latter three neuropathological markers of AD were shown to be markedly modulated by the presence of the apolipoprotein E4 (apoE4) allele in sporadic AD subjects. The apoE4 allele is a well-known risk factor for both sporadic and familial late-onset AD. It was shown that patients with two E4 alleles exhibit an earlier age of onset (Corder et al., 1993; Poirier et al., 1993), higher amyloid plaque counts (Rebeck, Reiter, Strickland, & Hyman, 1993; Schmechel et al., 1993), cerebrovascular amyloid deposition (Schmechel et al., 1993), and marked reductions in choline acetyltransferase (Allen et al., 1997; Arendt et al., 1997; Poirier, Delisle, et al., 1995), and nicotinic and nerve growth factor receptors (Arendt et al., 1997) density compared with non-E4 allele subjects.