Detection of pathologic prion protein in the olfactory epithelium in sporadic Creutzfeldt-Jakob disease.
BACKGROUND
Olfactory cortexes and the olfactory tracts are involved in sporadic Creutzfeldt-Jakob disease. We examined peripheral regions of the olfactory sensory pathway, including the olfactory mucosa, to assess whether pathologic infectious prion protein (PrPSc) is deposited in the epithelium lining the nasal cavity.


METHODS
We studied nine patients with neuropathologically confirmed sporadic Creutzfeldt-Jakob disease. We obtained the brain, the cribriform plate with the attached olfactory mucosa, and the surrounding respiratory epithelium at autopsy. Control samples of nasal mucosa were obtained post mortem or at biopsy from age-matched control subjects and from control patients with other neurodegenerative diseases. The olfactory and respiratory mucosa and the intracranial olfactory system were analyzed by light microscopy, immunohistochemistry, and Western blotting for pathological changes and for deposition of PrPSc.


RESULTS
In all nine patients with sporadic Creutzfeldt-Jakob disease, PrPSc was found in the olfactory cilia and central olfactory pathway but not in the respiratory mucosa. No PrPSc was detected in any of the tissue samples from the 11 controls.


CONCLUSIONS
Our pathological and biochemical studies show that PrPSc is deposited in the neuroepithelium of the olfactory mucosa in patients with sporadic Creutzfeldt-Jakob disease, indicating that olfactory biopsy may provide diagnostic information in living patients. The olfactory pathway may represent a route of infection and a means of spreading prions.
Zanusso
Gianluigi
G
Department of Neurologic and Visual Sciences, University of Verona, Verona, Italy.
Ferrari
Sergio
S
Cardone
Franco
F
Zampieri
Paolo
P
Gelati
Matteo
M
Fiorini
Michele
M
Farinazzo
Alessia
A
Gardiman
Marina
M
Cavallaro
Tiziana
T
Bentivoglio
Marina
M
Righetti
Pier Giorgio
PG
Pocchiari
Maurizio
M
Rizzuto
Nicola
N
Monaco
Salvatore
S
D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D001923:Brain Chemistry; D007562:Creutzfeldt-Jakob Syndrome / Q000473:pathology*; D004848:Epithelium / Q000737:chemistry; D005838:Genotype; D006801:Humans; D009831:Olfactory Mucosa / Q000737:chemistry*; D018620:PrPSc Proteins / Q000032:analysis* / Q000235:genetics / Q000276:immunology
D000911:Antibodies, Monoclonal; D018620:PrPSc Proteins