Apolipoprotein E isotype-specific effects in neurodegeneration

Apolipoprotein E (apoE) is an abundant lipoprotein that appears to be invol ved in membrane remodeling and repair and lipid redistribution, especially after neuronal injury. The three human isoforms of apoE protein, E2, E3, an d E4 show differential effects in the susceptibility to and outcome of seve ral neurodegenerative conditions. ApoE is the major susceptibility gene for sporadic and late-onset familiar Alzheimer's disease (AD). This review foc uses on apoE isotype-specific activities that impact neurodegeneration and neuroregeneration in direct and indirect mechanisms which arise from studie s of epidemiology, transgenic animals, cell culture and biochemistry. These include studies of apoE isotypes in amyloid and tau metabolism, lipid meta bolism, apoE metabolism, neurotoxicity and oxidative stress, neuroregenerat ion and neuronal sprouting, apoE expression and glial activation, and drug therapy interactions and phamacogenomics. One emerging theme is that apoE i sotypes may differ in the pathological mechanism by which they impact AD an d other neurodegenerative conditions, so that isotype-specific effects in a ny given apoE activity may be pathologically relevant for only one isotype.