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Previous Volume 348:711-719 February 20, 2003 Number 8 Next

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ABSTRACT

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 (PrP^Sc) 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 PrP^Sc.

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

Conclusions Our pathological and biochemical studies show that PrP^Sc 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.

Source Information

From the Departments of Neurologic and Visual Sciences (G.Z., S.F., M. Gelati, M.F., A.F., T.C., N.R., S.M.), Ear, Nose, and Throat (P.Z.), Morphologic and Biomedical Sciences (M.B.), and Agricultural and Industrial Biotechnologies (P.G.R.), Section of Clinical Neurology, University of Verona, Verona; the Laboratory of Virology, Istituto Superiore di Sanità, Rome (F.C., M.P.); and the Department of Pathology, University of Padua, Padua (M. Gardiman) — all in Italy.

Address reprint requests to Dr. Monaco at the Section of Clinical Neurology, Department of Neurologic and Visual Sciences, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, Italy, or at salvatore.monaco{at}mail.univr.it.

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