6,7 BSE and human prion diseases While all of the above may be predominantly of concern to veterinary medicine, a peculiar new variant of Creutzfeldt-Jakob disease (CJD, the pendant to BSE in humans) was first described in 19968

and has, thus far, taken a toll of 83 lives (Table I).9 As detailed below, there is good reason to suspect that new-variant Creutzfeldt-Jakob disease (nvCJD) represents the result Inhibitors,research,lifescience,medical of infection of humans with the BSE agent. Table I Incidence of new-variant Creutzfeldt-Jakob disease (nvCJD) in the United Kingdom since 1985, Although data for 2000 were incomplete at the time of writing, the incidence of nvCJD appears to have surpassed that of sporadically occurring Creutzfeldt-Jakob … Several striking characteristics of nvCJD set it aside from the “classical” sporadically occurring Creutzfeldt-Jakob disease Inhibitors,research,lifescience,medical (sCJD) that was described eight decades ago (Table II). 10,11 For one thing, sCJD typically affects elderly persons, whereas nvCJD has so far predominantly

hit very young people, with an age range spanning between 12 and 52 years. The reason for this age distribution remains unclear.12 Also, the clinical course of the two diseases is radically different: sCJD is typically a rapidly progressing illness leading to severe dementia and ultimately death within months, and sometimes even weeks. On the other hand, nvCJD Inhibitors,research,lifescience,medical tends to develop over a much more protracted period. Also, the predominant initial symptoms in nvCJD are personality changes and psychosis, rather than dementia.13 Table

II Diagnostic criteria for new-variant Inhibitors,research,lifescience,medical Creutzfeldt-Jakob disease (nvCJD).9 MRI, magnetic resonance imaging; sCJD, sporadically Inhibitors,research,lifescience,medical occurring Creutzfeldt-Jakob disease. Even under the microscope, the two diseases are very different from each other. sCJD is typically characterized by widespread LEE011 concentration vacuolation of the cortical neuropil, which, in its most extreme manifestation, makes the brain resemble a sponge (when observed under low-magnification microscopy), hence the designation “spongiform encephalopathy.” Instead, the hallmark of nvCJD is the extremely prominent accumulation of small spherical protein deposits, termed plaques, in the brain of the also affected individual. While some plaques can be seen in a minority of patients affected with sCJD, the plaques of nvCJD have a specific morphology that includes a characteristic rim of microvacuolated tissue. Further peculiarities of nvCJD include severe destruction of neurons in the thalamus, which is recognizable by noninvasive neuroimaging methods (the so-called pulvinar sign),14 as well as generalized colonization of the lymphoid organs by the infectious agent and deposition of the disease-associated prion protein (PrP) known as PrPSc (see below) in the germinal centers of the lymph nodes, tonsils, and spleen.