Neuroanatomic Profile of Polyglutamine Immunoreactivity inHuntington Disease Brains

Division of Neuropathology, Department of Pathology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9073, USA.
Journal of Neuropathology and Experimental Neurology (Impact Factor: 4.37). 04/2009; 68(3):250-61. DOI: 10.1097/NEN.0b013e318198d320
Source: PubMed

ABSTRACT A pathologic hallmark of Huntington disease (HD) is the presence of intraneuronal aggregates of polyglutamine-containing huntingtin protein fragments. Monoclonal antibody 1C2 is a commercial antibody to normal human TATA-binding protein that detects long stretches of glutamine residues. Using 1C2 as a surrogate marker formutant huntingtin protein, we immunostained 19 HD cases, 10 normal controls, and 10 cases of frontotemporal degeneration with ubiquitinated inclusions as diseased controls. In the HD cases, there was consistent 1C2 immunoreactivity in the neocortex, striatum, hippocampus, lateral geniculate body, basis pontis, medullary reticular formation, and cerebellar dentate nucleus. The normal and diseased controls demonstrated 1C2 immunoreactivity only in the substantia nigra, locus coeruleus, and pituitary gland. Staining of 5 HD cases and 5 normal controls revealed a less consistent and less diagnostically useful morphologic immunoreactivity profile. These results indicate that widespread 1C2 immunoreactivity is present in diverse central nervous system areas in HD, and that in the appropriate setting, 1C2 staining can be a useful tool in the postmortem diagnosis of HD when neuromelanin-containing neuronal populations are avoided.

    • "The inclusions are present prior to symptomatic development of the disease in the human brain and found throughout the cortex, but less frequently in the striatum [92] [93] [94] [95] [96]. Within the cortex, the cells tend to display combinations of nuclear and cytoplasmic as well as neuropil aggregations [95] with the highest levels of intranuclear inclusions found in juvenile cases which tend to have relatively very high CAG repeat Fig. 2. Photomicrographs illustrating the pyramidal neurons in layer III in the primary motor cortex (A–C) and anterior cingulate cortex (D–F) of normal (A, D) and Huntington's disease cases (B, C; E, F). The images illustrate cases with " mainly motor " (B, E), and " mainly mood " (C, F) symptom profiles. "
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