Organ distribution of prion proteins in variant Creutzfeldt-Jakob disease

In this article we give an overview of the transmissible spongiform encephalopathies, with emphasis on the evidence for the distribution of abnormal prions in tissues. The normal prion protein is distributed ubiquitously throughout human body tissues. Endogenous expression of the normal prion protein, as well as auxiliary proteins, plays a part in accumulation of the abnormal prion protein. As exemplified by variant Creutzfeldt-Jakob disease (vCJD) the abnormal prion protein can accumulate in the host lymphoid system, in particular the follicular dendritic cells. The route for the disease-related prion neuroinvasion is likely to involve the peripheral nervous system. An alternative route may involve blood constituents. Both animal studies and studies on vCJD patients suggest a potential for abnormal prion distribution in several peripheral tissues other than the lymphoreticular system. In human beings the abnormal prion has been reported in the brain, tonsils, spleen, lymph node, retina, and proximal optic nerve. Infectivity, although present in peripheral tissues, is at lower levels than in the central nervous system (CNS). Animal models suggest that the growth of infectivity in the CNS is likely to be gradual with maximum values during the clinical phase of disease. That tissues may harbour the abnormal prion, at different levels of infectivity, during the incubation period of the disease raises concerns of iatrogenic transmission of the disease either after surgery, blood transfusion, or accidental organ transplantation from donors in the preclinical phase of the disease.