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Disease‐associated proteins are thought to propagate along neuronal processes in neurodegenerative diseases. To detect disease‐associated prion protein (PrP Sc ) in the vagus nerve in different forms and molecular subtypes of Creutzfeldt–Jakob disease (CJD), we applied 3 different anti‐PrP antibodies. We screened the vagus nerve in 162 sporadic and 30 genetic CJD cases. Four of 31 VV‐2 type sporadic CJD and 7 of 30 genetic CJD cases showed vagal PrP Sc  immunodeposits with distinct morphology. Thus, PrP Sc  in CJD affects the vagus nerve analogously to α‐synuclein in Parkinson disease. The morphologically diverse deposition of PrP Sc  in genetic and sporadic CJD argues against uniform mechanisms of propagation of PrP Sc . Ann Neurol 2019;85:782–787

Accumulation of prion protein in the vagus nerve in creutzfeldt–jakob disease