Disease associated prion protein may deposit in the peripheral nervous system in human transmissible spongiform encephalopathies

There is increasing evidence indicating involvement of the peripheral nervo us system (PNS) in the pathogenesis of transmissible spongiform encephalopa thies (TSEs). Immunocytochemically detectable deposits of TSE-specific abno rmal prion protein (PrPsc) are considered as a surrogate marker for infecti vity. We used anti-PrP immunocytochemistry to trace PrPsc deposition in spi nal and enteric ganglia, and peripheral nerve in Creutzfeldt-Jakob disease (CJD), Gerstmamn-Straussler-Scheinker disease (GSS), and fatal familial ins omnia. Discrete PrPsc deposits were detectable only in a few posterior root nerve fibers in an adaxonal location in one of nine CJD and the one GSS pa tients examined. Follicular dendritic cells of the gut and enteric nervous system were not labeled. Thus, PrPsc may spread to the PNS in different for ms of human prion disease. Ln contrast to our observations in experimental scrapie (Groschup et al., Acta Neuropathol, this issue), the deposits were scant. Possible explanations for this discrepancy comprise strain differenc e, or centripetal (experimental scrapie) versus centrifugal (sporadic and g enetic human prion diseases) spread of PrPsc, resulting in different patter ns and amounts of PrPsc accumulation in the PNS.