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Abnormal prion proteins may be present in the nasal mucosa of patients with Creutzfeldt-Jakob disease, according to a study of nine patients. This disease is the human version of mad cow disease, which is technically called bovine spongiform encephalopathy, or BSE. The presence of the abnormal prion protein responsible for these two diseases in the nose means the protein may be transmitted by contaminated surgical instruments. A nasal biopsy could also be a means of diagnosing the disease in its early stages.

IgM monoclonal gammopathy, a disorder characterized by abnormal multiplication of white blood cells producing a single (monoclonal) antibody of the IgM class, is frequently associated with polyneuropathy, nerve damage affecting several nerves and leading to weakness, tremor, and loss of sensation. The IgM antibody (M protein) of some patients actually reacts with components of the myelin sheath, the material that covers nerves and insulates them, allowing normal electrical transmission. It is possible that the demyelination, or loss of myelin, associated with this condition is the result of attack by M proteins. The mechanisms by which this might happen were studied. One way antibodies can cause cell damage is by means of the complement (C) proteins, a group of proteins activated in a chain-reaction manner (cascade) by antibody-antigen complexes. The antibodies involved in these complexes are called complement-fixing antibodies, and when they bind to the antigen they recognize, the molecular unit so formed can activate the first complement molecule to begin the cascade. The molecule formed as the last step in the cascade is called the terminal-complement complex; it is capable of causing the death of the cell to which the antibody has bound by introducing pores in its membrane. This is clearly of use if the antigen is dangerous to the body, but dysfunctional if the antigen is a component of the body's own myelin. The IgM molecules of seven IgM monoclonal gammopathy patients were studied. Six were found to have IgMs that reacted with molecules known to be associated with myelin, while the seventh had an M protein that reacted with an unidentified myelin component. Other methods demonstrated that these M proteins were preferentially deposited on the majority of myelinated fibers of nerves, and that some of the nerve fibers also had complement molecules on their surfaces. The presence of complement proteins from both early (C1q) and late (C9 neoantigen) stages of the cascade suggests that the demyelination in these patients may, indeed, be the result of antibody deposition and mediated by complement. None of these compounds were found on nerves from seven normal subjects, seven patients with hereditary sensorimotor neuropathy, or seven patients with diabetic neuropathy. Additional details regarding the role of complement in the pathogenesis of this type of polyneuropathy are provided. (Consumer Summary produced by Reliance Medical Information, Inc.)

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. N Engl J Med 2003;348:711-9. [ABSTRACT FROM AUTHOR]