Given the separation of the brain's cholesterol/lipid metabolism from the rest of the body, a critical role of cholesterol for neuronal functions, and a high abundance of cholesterol in the brain (estimated 25% of total body cholesterol), ApoE and CLU/ApoJ may thus function as the brain-specific counterparts of injury/damage response, potentially explaining why certain genetic variants of these apolipoproteins are associated with the AD risk. The gene discussed is APOE; the disease is Alzheimer disease.