Paradigm shifts in XXXX and other @entity179 : the emerging role of oligomeric assemblies.

@entity1 @entity527 @entity303 @entity746 @entity14755 @entity191 @entity477 @entity1579 @entity179 @entity195 @entity204 @entity528 @entity2359
@entity195 ( @entity195 ) is a progressive, @entity179 characterized by @entity527 in the cerebral neuropil and vasculature. These @entity527 comprise predominantly fragments and full-length (40 or 42 residue) forms of the amyloid beta-protein ( @entity477 ) organized into fibrillar assemblies. Compelling evidence indicates that factors that increase overall @entity477 production or the ratio of longer to shorter forms, or which facilitate deposition or inhibit elimination of @entity527 , cause @entity195 or are risk factors for the disease. In vitro studies have demonstrated that fibrillar @entity477 has potent @entity2359 effects on cultured neurons. In vivo experiments in non- @entity1 primates have demonstrated that @entity477 fibrils directly cause pathologic changes, including tau hyperphosphorylation. In concert with histologic studies revealing a lack of tissue injury in areas of the neuropil in which non-fibrillar deposits were found, these data suggested that fibril assembly was a prerequisite for @entity477 -mediated @entity2359 in vivo. Recently, however, both in vitro and in vivo studies have revealed that soluble, oligomeric forms of @entity477 also have potent @entity2359 activities, and in fact, may be the proximate effectors of the @entity528 and @entity204 occurring in @entity195 . A paradigm shift is thus emerging that necessitates the reevaluation of the relative importance of polymeric (fibrillar) vs. oligomeric assemblies in the pathobiology of @entity195 . In addition to @entity195 , an increasing number of @entity179 , including @entity191 , familial British @entity303 , @entity14755 , @entity746 , and @entity1579 , are associated with abnormal protein assembly processes. The archetypal features of the assembly-dependent neuropathogenetic effects of @entity477 may thus be of relevance not only to @entity195 but to these other disorders as well.
