The role of apolipoprotein E in Alzheimer's disease, acute brain injury and cerebrovascular disease: evidence of common mechanisms and utility of animal models

The epsilon 4 allele of apolipoprotein E (APOE denotes gene; apoE denotes p rotein) is a major risk factor for Alzheimer's disease (AD). More recent ev idence indicates an association with a poor outcome after acute brain injur y including that due to head trauma and intracerebral hemorrhage. APOE gene polymorphism also influences the risk of hemorrhage in cerebral amyloid an giopathy. These diverse brain disorders seem to have some mechanisms in com mon. The multiplicity of the roles of apoE within the central nervous syste m is currently being unraveled. For example, apoE can interact with amyloid beta-protein and tau, proteins central to the pathogenesis of AD. In addit ion to these effects, it is proposed that one of the major functions of apo E is to mediate neuronal protection, repair and remodeling. In all of the d ifferent roles proposed, there are marked apoE-isoform specific differences . Although it remains to be clarified which is the most important mechanism (s) in each disorder in which apoE is involved, these isoform specific diff erences seem to underly a genetically determined susceptibility to outcome from acute brain injury and to AD with APOE epsilon 4 conferring relative v ulnerability. This review focuses on apoE research, from clinical studies t o animal models, in AD, acute brain injury and cerebrovascular disease and explores the common mechanisms that may explain some of the complex underly ing neurobiology. (C) 2000 Elsevier Science Inc. All rights reserved.