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

• Published in: Neurobiology of aging 2000-03, Vol.21 (2), p.245-255
• Main Authors: Horsburgh, Karen, McCarron, Mark O, White, Fiona, Nicoll, James A.R
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - etiology; Alzheimer Disease - physiopathology; Alzheimer’s disease; Animal models; Animals; Apolipoprotein E; Apolipoproteins E - genetics; Apolipoproteins E - physiology; Biological and medical sciences; Brain Injuries - physiopathology; Cerebrovascular disease; Cerebrovascular Disorders - physiopathology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Humans; Medical sciences; Neurology; Transgenic mice; Trauma; Vascular dementia
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/S0197-4580(00)00097-X

The ϵ4 allele of apolipoprotein E ( APOE denotes gene; apoE denotes protein) is a major risk factor for Alzheimer’s disease (AD). More recent evidence indicates an association with a poor outcome after acute brain injury including that due to head trauma and intracerebral hemorrhage. APOE gene polymorphism also influences the risk of hemorrhage in cerebral amyloid angiopathy. These diverse brain disorders seem to have some mechanisms in common. The multiplicity of the roles of apoE within the central nervous system is currently being unraveled. For example, apoE can interact with amyloid β-protein and tau, proteins central to the pathogenesis of AD. In addition to these effects, it is proposed that one of the major functions of apoE is to mediate neuronal protection, repair and remodeling. In all of the different 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 differences seem to underly a genetically determined susceptibility to outcome from acute brain injury and to AD with APOE ϵ4 conferring relative vulnerability. This review focuses on apoE research, from clinical studies to animal models, in AD, acute brain injury and cerebrovascular disease and explores the common mechanisms that may explain some of the complex underlying neurobiology.