Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and universally fatal transmissible spongiform encephalopathy caused by prions -- misfolded isoforms (PrPSc) of normal cellular prion protein (PrPC). PrPSc acts as a template, converting normal PrPC into the pathological conformation through a self-propagating cascade. The misfolded proteins are resistant to proteases, heat, radiation, and standard sterilization. Accumulation of PrPSc causes neuronal vacuolation (spongiform change), astrogliosis, and neuronal death without inflammatory infiltrate. Forms include sporadic CJD (85%, mean age 65, unknown trigger), familial/genetic CJD (10-15%, PRNP gene mutations), iatrogenic CJD (contaminated surgical instruments, dura mater grafts, cadaveric pituitary hormones), and variant CJD (vCJD, bovine spongiform encephalopathy/mad cow disease, younger patients, psychiatric symptoms, 'florid plaques').