Recently, the inheritance of particular alleles of apolipoprotein E (apoE) has been found to correlate with the rates of progression of age- related cognitive decline. Because in vitro and anatomical data have suggested that different apoE isoforms have differential effects on processes such synaptic remodeling, neurite extension, and microtubular aggregation, a variety of hypotheses have been raised regarding the mechanism of its effects on cognitive aging. Here we propose developing a biological tool that will be useful in dissecting out the isoform- specific contributions of apoE in vivo, in the aging brain. Adeno- associated viral vectors will be generated that express the three apoE alleles E2, E3, and E4. Adeno-associated virus is a DNA parvovirus that has the unique ability transfer foreign genes in the absence of contaminating viral proteins. Because adeno-associated virus can produce long-term (greater than 8 months in some cases) stable gene expression, it is particularly suited for use in animal models of aging.
