Multiple prion types in the same brain

Transmissible spongiform encephalopathies (TSEs) are rare neurologic disorders that bear some resemblance to more common neurodegenerative conditions, such as Alzheimer’s disease and Parkinson’s disease. TSEs, however, are transmissible, whereas there is no convincing evidence that AD or PD are caused by transmissible agents.1 Conversely, TSEs, AD, and PD are all associated with progressive accumulation of fibrillar proteins in the brain. In TSE, most evidence suggests that the prion protein (PrP) is the cause of the disease and the transmissible agent.2 In AD, two types of fibrillar proteins are involved; extracellular amyloid deposits composed of Aβ, a proteolytic fragment of the amyloid precursor protein, and intracellular neurofibrillary inclusions composed of τ protein, a microtubule associated protein. In PD, intracellular fibrillar protein aggregates of synuclein form Lewy bodies, the histologic hallmark of PD. This tendency of normal cellular proteins to acquire novel attributes, which may be related to conformational changes and that favor formation of fibrillar, amyloid-like aggregates, may be a common mechanism in the pathogenesis of these disorders.3

The TSEs are most often sporadic disorders, but rare hereditary and iatrogenic variants are also recognized.1 The most common sporadic TSE is Creutzfeldt-Jakob disease (CJD). Hereditary forms include Gerstmann-Straüssler-Sheinker syndrome (GSS), familial CJD, and fatal familial insomnia (FFI). The most common iatrogenic form of TSE resulted from the administration of a growth hormone derived from cadaver pituitaries, a practice that is no longer used. Of great public health concern is the epidemic of bovine spongiform encephalopathy (BSE), which appears to be etiologically linked to a new …