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Intraneuronal polyglutamine aggregates are present in diverse CNS locations in Huntington disease
Author(s) -
Herndon Emily S,
Hladik Christa L,
Shang Ping,
Burns Dennis K,
White Charles L
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a23-a
Subject(s) - pathology , locus coeruleus , biology , entorhinal cortex , neuropathology , white matter , pontine nuclei , brainstem , neuroscience , central nervous system , hippocampus , medicine , disease , radiology , magnetic resonance imaging
Huntington disease (HD) is caused by the expansion of a CAG repeat within the HD gene yielding an abnormal huntingtin protein (Htt) with an expanded polyglutamine repeat near the N‐terminus. A fragment of the protein containing this repeat accumulates in neurons, forming aggregates. While the presence of these aggregates is a marker for HD, the effect of Htt aggregates is still unknown. To identify locations in the CNS of HD patients that contain these aggregates, we employed a monoclonal antibody to a 38 polyglutamine repeat (Chemicon) to stain paraffin sections of various regions of formalin‐fixed, postmortem CNS tissue from 12 HD patients. Sections were treated with formic acid prior to immunostaining. Abnormal polyglutamine immunoreactivity was identified in cortical neurons of all 4 cerebral lobes, entorhinal cortex, subiculum, lateral geniculate body, locus coeruleus, dentate and pontine nuclei, and spinal cord grey matter. In the medulla, multiple cranial nerve nuclei and scattered neurons of the reticular formation demonstrated staining. Areas that failed to stain included the pituitary and pineal glands, white matter, and cerebellar cortex. These data indicate that abnormal Htt can be found in diverse CNS locations in a distribution pattern that is non‐random and reproducible and suggest that HD may affect populations of neurons that were not previously known to be involved in that disorder. Supported in part by NIH ADC grant AG12300, the Winspear Family Center for Research on the Neuropathology of Alzheimer Disease, and the McCune Foundation.