TY - JOUR T1 - Nuclear and Neuropil Aggregates in Huntington’s Disease: Relationship to Neuropathology JF - The Journal of Neuroscience JO - J. Neurosci. SP - 2522 LP - 2534 DO - 10.1523/JNEUROSCI.19-07-02522.1999 VL - 19 IS - 7 AU - Claire-Anne Gutekunst AU - Shi-Hua Li AU - Hong Yi AU - James S. Mulroy AU - Stefan Kuemmerle AU - Randi Jones AU - David Rye AU - Robert J. Ferrante AU - Steven M. Hersch AU - Xiao-Jiang Li Y1 - 1999/04/01 UR - http://www.jneurosci.org/content/19/7/2522.abstract N2 - The data we report in this study concern the types, location, numbers, forms, and composition of microscopic huntingtin aggregates in brain tissues from humans with different grades of Huntington’s disease (HD). We have developed a fusion protein antibody against the first 256 amino acids that preferentially recognizes aggregated huntingtin and labels many more aggregates in neuronal nuclei, perikarya, and processes in human brain than have been described previously. Using this antibody and human brain tissue ranging from presymptomatic to grade 4, we have compared the numbers and locations of nuclear and neuropil aggregates with the known patterns of neuronal death in HD. We show that neuropil aggregates are much more common than nuclear aggregates and can be present in large numbers before the onset of clinical symptoms. There are also many more aggregates in cortex than in striatum, where they are actually uncommon. Although the striatum is the most affected region in HD, only 1–4% of striatal neurons in all grades of HD have nuclear aggregates. Neuropil aggregates, which we have identified by electron microscopy to occur in dendrites and dendritic spines, could play a role in the known dendritic pathology that occurs in HD. Aggregates increase in size in advanced grades, suggesting that they may persist in neurons that are more likely to survive. Ubiquitination is apparent in only a subset of aggregates, suggesting that ubiquitin-mediated proteolysis of aggregates may be late or variable. ER -