Niemann-Pick type C (NPC) is a genetic disorder affecting cholesterol transport that is accompanied by chronic progressive neurodegeneration. In animal models of NPC, ApoD expression is increased in the plasma and the brain. In rats, ApoD expression increases in the hippocampus after enthorinal cortex lesioning. ApoD mRNA and protein increases in the ipsilateral region of hippocampus as early as 2 days post-lesion (DPL), remains high for 10 days and returns to normal after 14 DPL, a period considered necessary for a complete reinervation. Similar results are obtained after injection of kainic acid, an analog of glutamic acid which causes a severe neurodegenerative injury in the hippocampus or after experimentally-induced stoke. ApoD expression is also increased in the aging brain. Altogether, these data suggest that ApoD plays an important role in neural preservation and protection.