Prion type 2 selection in sporadic Creutzfeldt\u2013Jakob disease affecting peripheral ganglia

Anna Hofmann,Wiebke M Jürgens-Wemheuer,Walter J Schulz-Schaeffer,Arne Wrede

doi:10.1186/s40478-021-01286-4

Abstract

In sporadic Creutzfeldt–Jakob disease (sCJD), the pathological changes appear to be restricted to the central nervous system. Only involvement of the trigeminal ganglion is widely accepted. The present study systematically examined the involvement of peripheral ganglia in sCJD utilizing the currently most sensitive technique for detecting prions in tissue morphologically. The trigeminal, nodose, stellate, and celiac ganglia, as well as ganglia of the cervical, thoracic and lumbar sympathetic trunk of 40 patients were analyzed with the paraffin-embedded tissue (PET)-blot method. Apart from the trigeminal ganglion, which contained protein aggregates in five of 19 prion type 1 patients, evidence of prion protein aggregation was only found in patients associated with type 2 prions. With the PET-blot, aggregates of prion protein type 2 were found in all trigeminal (17/17), in some nodose (5 of 7) and thoracic (3 of 6) ganglia, as well as in a few celiac (4 of 19) and lumbar (1 of 5) ganglia of sCJD patients. Whereas aggregates of both prion types may spread to dorsal root ganglia, more CNS-distant ganglia seem to be only involved in patients accumulating prion type 2. Whether the prion type association is due to selection by prion type-dependent replication, or due to a prion type-dependent property of axonal spread remains to be resolved in further studies.

Highlights

Prion diseases or transmissible spongiform encephalopathies are neurodegenerative disorders and always fatal
While prion protein aggregates were never detectable in samples of the vagus (See figure on page.) Fig. 1 PrPSc aggregates in peripheral ganglia of sporadic Creutzfeldt–Jakob disease (sCJD) patients detected by paraffin-embedded tissue (PET)-blot and immunohistochemistry
Prion protein aggregates within several ganglia are visualized by conventional immunohistochemistry (A, C, E), and with the PET-blot technique (B, D, F)

Summary

Introduction

Prion diseases or transmissible spongiform encephalopathies are neurodegenerative disorders and always fatal. The infectious agent seems to be an unconventional one as it appears that the pathologic misfolded form (PrPSc) of a physiological protein (PrPC) is responsible for its transmissibility. With an incidence of 1–2 in 1,000,000, Creutzfeldt–Jakob disease (CJD) is the most common prion disease in humans. Several animal models with orally transmitted prion diseases reveal an involvement of the peripheral nervous system, mainly of peripheral ganglia. The orally scrapie-challenged hamster model gave insights into the temporo-spatial spread of agents initiating from enteric regions, i.e. the myenteric and submucosal plexuses of the ileum [24]. The authors later described the existence of two centripetal anatomical routes, where pathological prion protein was first detectable in autonomic structures and later in sensory ones.

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