This finding suggests that HS biosynthetic enzymes, such as Ndst1, may be therapeutic targets for select neurodegenerative diseases in which extracellular amyloid plaques develop, including familial prion disease [Gerstmann-Sträussler-Scheinker disease (GSS)], vCJD, as well as Alzheimer’s disease. Here, NDST1 is linked to variant Creutzfeldt-Jakob disease.