Protein Aggregates

In all four cases reported above, and in four other cases examined by our group, there were intranuclear aggregates that stained with anti-ubiquitin antibodies and an antibody (1C2) with partial specificity for long polyglutamine tracts [25] (Fig. 3). In the index case, aggregates were relatively infrequent, and were more common in striatum then cortex. They did not stain with anti-huntingtin antibodies. In the second case [26], aggregates were most common in the insula of the cortex, and were not detected in the basal ganglia. Interestingly, the inclusions stained for torsinA, but not for tau, alpha-synuclein, or p53. In the third case, scattered aggregates were found in multiple brain regions, and were generally most frequent near, but not in, those regions with the greatest neurodegeneration. In the fourth case, aggregates stained with anti-ubiquitin antibodies were found in the nuclei of neurons in multiple brain regions. Aggregates ranged in size from punctate to 5mm, and aggregate frequency did not appear to correlate with the extent of neuronal loss. In all cases,

Fig. 3 Protein aggregates in HDL2. (a) Aggregates in cortical neurons detected by anti-ubiquitin antibodies. (b, c) Aggregates in cortex detected with anti-torsin A antibodies at higher power (x60) and lower power (x20). (d) Anti-torsin A staining of hippocampal granule cells. (e) 1C2 staining of aggregate, as detected by confocal microscoping using fluorochrome-labeled immuno-reactivity (arrow indicates cytoplasmic lipofuscin). (f) Electron micrograph of protein aggregates (x20,000). (Figure and portions of the figure legend, are reprinted with permission from Walker et al. [26].)

Fig. 3 Protein aggregates in HDL2. (a) Aggregates in cortical neurons detected by anti-ubiquitin antibodies. (b, c) Aggregates in cortex detected with anti-torsin A antibodies at higher power (x60) and lower power (x20). (d) Anti-torsin A staining of hippocampal granule cells. (e) 1C2 staining of aggregate, as detected by confocal microscoping using fluorochrome-labeled immuno-reactivity (arrow indicates cytoplasmic lipofuscin). (f) Electron micrograph of protein aggregates (x20,000). (Figure and portions of the figure legend, are reprinted with permission from Walker et al. [26].)

the aggregates were round to oval in shape, and resembled those seen in HD. Aggregates outside of the nucleus, as seen in HD and other polyglutamine disorders, have not yet been reported in HDL2.

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