Abstract: Compounds, compositions and therapeutic methods are disclosed for the treatment of the central nervous system. The compounds are derived from the disclosed assay system which tests compounds for their ability to effect neuronal remodeling and neurite outgrowth. The assay uses cell cultures which have been genetically engineered to effect the expression of apoE3 and/or apoE4. A test compound is brought into contact with engineered neuronal cells in the presence of a lipid such as &bgr;-VLDL to determine the affects of the compound, if any, on the neuronal remodeling and neurite outgrowth. Compounds found to promote neurite outgrowth are used therapeutically in the treatment of diseases and/or damage to the central nervous system.

Abstract: The present invention features non-human transgenic animal models for gene function, wherein the transgenic animal is characterized by having altered endogenous apolipoprotein E gene function and a transgene for an exogenous human apolipoprotein E isoform. The transgenic animals may be either homozygous or heterozygous for the transgene. The invention also features methods for using non-human transgenic animal models for the study of apolipoprotein E-mediated pathologies and the identification of compounds and therapies for such pathologies.