Detection of Pathologic Prion Protein in the Olfactory Epithelium in Sporadic Creutzfeldt–Jakob Disease

Zanusso, Gianluigi; Ferrari, Sergio; Cardone, Franco; Zampieri, Paolo; Gelati, Matteo; Fiorini, Michele; Farinazzo, Alessia; Gardiman, Marina Paola; Cavallaro, Tiziana; Bentivoglio, Marina; Righetti, Pier Giorgio; Pocchiari, Maurizio; Rizzuto, N.; Monaco, Salvatore

doi:10.1056/nejmoa022043

Cited by 143 publications

(97 citation statements)

References 35 publications

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“…Films were scanned by using a densitometer (GS-710; Bio-Rad). The relative amounts of PrP Sc distribution were calculated as previously described (18).…”

Section: Methodsmentioning

confidence: 99%

Identification of a second bovine amyloidotic spongiform encephalopathy: Molecular similarities with sporadic Creutzfeldt-Jakob disease

Casalone

Zanusso

Acutis

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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412

406

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Transmissible spongiform encephalopathies (TSEs), or prion diseases, are mammalian neurodegenerative disorders characterized by a posttranslational conversion and brain accumulation of an insoluble, protease-resistant isoform (PrP Sc ) of the host-encoded cellular prion protein (PrP C ). Human and animal TSE agents exist as different phenotypes that can be biochemically differentiated on the basis of the molecular mass of the protease-resistant PrP Sc fragments and the degree of glycosylation. Epidemiological, molecular, and transmission studies strongly suggest that the single strain of agent responsible for bovine spongiform encephalopathy (BSE) has infected humans, causing variant Creutzfeldt-Jakob disease. The unprecedented biological properties of the BSE agent, which circumvents the so-called ''species barrier'' between cattle and humans and adapts to different mammalian species, has raised considerable concern for human health. To date, it is unknown whether more than one strain might be responsible for cattle TSE or whether the BSE agent undergoes phenotypic variation after natural transmission. Here we provide evidence of a second cattle TSE. The disorder was pathologically characterized by the presence of PrP-immunopositive amyloid plaques, as opposed to the lack of amyloid deposition in typical BSE cases, and by a different pattern of regional distribution and topology of brain PrP Sc accumulation. In addition, Western blot analysis showed a PrP Sc type with predominance of the low molecular mass glycoform and a protease-resistant fragment of lower molecular mass than BSE-PrP Sc . Strikingly, the molecular signature of this previously undescribed bovine PrP Sc was similar to that encountered in a distinct subtype of sporadic Creutzfeldt-Jakob disease.

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“…Films were scanned by using a densitometer (GS-710; Bio-Rad). The relative amounts of PrP Sc distribution were calculated as previously described (18).…”

Section: Methodsmentioning

confidence: 99%

Identification of a second bovine amyloidotic spongiform encephalopathy: Molecular similarities with sporadic Creutzfeldt-Jakob disease

Casalone

Zanusso

Acutis

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

412

406

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“…30 The pathological infectious prion protein P r P Sc is consistently found in the olfactory cilia, receptor cells, bulbs, tracts, and primary olfactory cortices of patients with Creutzfeldt-Jakob disease, but not in the retina, optic nerves, or respiratory mucosa. 31 A number of patients with this disease first present to the clinician with anosmia or complaints of taste and smell loss. 31,32 Although a wide range of xenobiotics can become incorporated into olfactory receptor cells, including dyes and amino acids, not all are transported across the synaptic membrane to neighboring cells.…”

Section: Evidence That Xenobiotics Can Enter the Brain Via The Olfactmentioning

confidence: 99%

“…31 A number of patients with this disease first present to the clinician with anosmia or complaints of taste and smell loss. 31,32 Although a wide range of xenobiotics can become incorporated into olfactory receptor cells, including dyes and amino acids, not all are transported across the synaptic membrane to neighboring cells. For many that cross the synapse, including a number of viruses, internalization into the cell initially occurs via receptormediated endocytosis.…”

Section: Evidence That Xenobiotics Can Enter the Brain Via The Olfactmentioning

confidence: 99%

The olfactory vector hypothesis of neurodegenerative disease: Is it viable?

Doty

2008

Annals of Neurology

355

279

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Environmental agents, including viruses, prions, and toxins, have been implicated in the cause of a number of neurodegenerative diseases, most notably Alzheimer's and Parkinson's diseases. The presence of smell loss and the pathological involvement of the olfactory pathways in the formative stages of Alzheimer's and Parkinson's diseases, together with evidence that xenobiotics, some epidemiologically linked to these diseases, can readily enter the brain via the olfactory mucosa, have led to the hypothesis that Alzheimer's and Parkinson's diseases may be caused or catalyzed by agents that enter the brain via this route. Evidence for and against this concept, the “olfactory vector hypothesis,” is addressed in this review. Ann Neurol 2008;63:7–15

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“…In this context it is noteworthy that pathological prion protein was found in the olfactory cilia and basal cells of the olfactory mucosa of sCJD patients, as well as in the olfactory bulb and olfactory tract. 40,41 However, it was hitherto never clearly documented that olfactory receptor neurons represent an entry site for infectious prions; this might also be due to the sensitivity threshold of detection assays.…”

Section: Aerosolsmentioning

confidence: 99%