Human apolipoprotein E isoform-specific differences in neuronal sprouting in organotypic hippocampal culture

The apolipoprotein E (ApoE) epsilon 4 allele is a major risk factor for neu rodegenerative conditions, including Alzheimer's disease. A role for ApoE i s implicated in regeneration of synaptic circuitry after neural injury. In the in vitro mouse organotypic hippocampal slice culture system, we previou sly showed that cultures derived from ApoE-knockout mice are defective in m ossy fiber sprouting into the dentate gyrus molecular layer. This sprouting defect was rescued in cultures from transgenic mice expressing ApoE3 under the control of the human promoter and in ApoE-knockout cultures treated wi th ApoE3-conditioned media. Although the ApoE3 transgene fully restored spr outing, ApoE4 restored sprouting to only 58% of ApoE3 levels. These data in dicate that ApoE isoform-specific effects on neuroregeneration may contribu te to its genetic risk for Alzheimer's disease.