Ultrastructural localization and progressive formation of neuropil aggregates in Huntington's disease transgenic mice

How aggregates of polyglutamine proteins, are involved in the neurological symptoms of glutamine repeat diseases is unknown. We show that huntingtin a ggregates are present in the neuronal processes of transgenic mice that exp ress exon 1 of the Huntington's disease (HD) gene. Unlike aggregates in the nucleus, these neuropil aggregates are usually smaller and are not ubiquit inated. Electron microscopy reveals many neuropil aggregates in axons and a xon terminals. Huntingtin aggregates in the axon terminal are colocalized w ith some synaptic vesicles, implying that they may affect synaptic transmis sion and neuronal communication. The formation of neuropil aggregates is hi ghly correlated with the development of neurological symptoms. The present study raises the possibility that neuropil aggregates may cause a dysfuncti on in neuronal communication and contribute to the neurological symptoms of HD.