Ubiquitin immunoelectron microscopy of dystrophic neurites in cerebellar senile plaques of Alzheimer's disease

Abstract

Senile plaques are present in the cerebellum of most Alzheimer patients. They are composed of beta-amyloid deposits lacking neurites detectable with immunocytochemistry for neurofilament, tau and paired helical filament proteins. Recent studies, however, have shown that cerebellar plaques usually contain round structures that are reactive with ubiquitin antibodies. In this immunoelectron microscopic study, the nature of these structures is explored. Ubiquitin-positive structures in cerebellar senile plaques were composed of degenerating neurites that contained membranous and vesicular dense bodies, but no paired helical filaments. A minority of the neurites contained finely granular material. Thus, cerebellar plaques are associated with neuritic degeneration, and the neurites in cerebellar plaques resemble dystrophic neurites in senile plaques of non-demented elderly subjects and subjects with non-Alzheimer dementias. They differ from some of the neurites in senile plaques in the neocortex in Alzheimer's disease by the absence of paired helical filaments. These results suggest that the same mechanisms involved in the generation of dystrophic neurites in pathological aging are involved in generating dystrophic neurites in the cerebellum in Alzheimer's disease.