Variant Creutzfeldt-Jakob disease is caused by a tiny protein, called a prion. The prion is present in cattle that have bovine spongiform encephalopathy (BSE). Humans are thought to become infected by eating cattle that are infected with the prion.

Prion proteins occur in both a normal form, which is a harmless protein found in the body's cells, and in an infectious form, which causes Variant Creutzfeldt-Jakob disease. The infectious form of the protein has a different folded shape than the normal form. Once the abnormal prions appear, they clump together within cells and somehow trigger cell death.