The cortical neuritic pathology of Huntington's disease

Abstract

We have studied the brains of 10 patients with clinically and pathologically defined Huntington's disease and graded the degree of striatal pathology according to the Vonsattel grading system. Sections from nine cerebral cortical areas (Brodmann areas 8, 10, 24, 33, 28, 38, 7, 39, 18), the cerebellum, hypothalamus, medulla and caudate nucleus were stained with antibodies to ubiquitin and ubiquitin C-terminal hydrolase (PGP 9.5). Dystrophic neurites, immunoreactive with ubiquitin and PGP 9.5 were detected in all cortical areas, in layers 3, 5 and 6, of all brains studied. No dystrophic neurites were found in subcortical areas or cerebellum. Sections from cortical areas 8 and 24 from the two brains with the most and least ubiquitin-immunoreactive neurites were stained with antibodies to beta-amyloid precursor protein, tau, glial fibrillary acidic protein, neurofilament protein, alpha B crystallin, GABA, cholecystokinin and somatostatin. The dystrophic neurites were found to also react with beta-amyloid precursor protein. Electron microscopy showed the abnormal neurites to contain granulofilamentous material. Granular deposits with a diameter of 40-100 nm were interspersed between randomly orientated 'fuzzy' or coated, straight or slightly curved filaments measuring 10-15 nm in diameter. These structures have not been seen in control brain and differ from age-related neuritic degeneration and neurites associated with amyloid. Immunohistochemically these structures most resemble CA 2/3 neurites seen in Lewy body disease, and, ultrastructurally, the intraneuronal filamentous inclusions in motor neuron disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Nonapoptotic neurodegeneration in a transgenic mouse model of Huntington's disease

“…However, this cortical area has been demonstrated to exhibit hypometabolism in patients with HD, studied by a variety of noninvasive functional imaging methods (31). Similarly, neuropathological studies have highlighted this area as one exhibiting prominent neurite pathology in this disease (32,33). Our studies, confirmed by results of the studies of postmortem material from HD patients, suggests that further investigation of the anterior cingulate cortex in HD is clearly warranted.…”

Axonopathy in Huntington's disease

“…Neuropathological evidence of neuritic dysfunction, Ub and APP immunoreactivity and the presence of aggregates in the neuropil led to the hypothesis that axonal transport defects were the basis of neuronal dysfunction since the early studies (Jackson, et al, 1995). Abnormalities Future therapeutic strategies in HD must aim at targeting early synaptic and axonal dysfunctions as well as at fighting neurodegeneration at the later stages of the pathology.…”

Retrograde Amnesia in Dementia: Comparison of HIV-Associated Dementia, Alzheimer's Disease, and Huntington's Disease.

“…However, the inability of the HIV-D and HD groups to benefit from cuing to the same degree as the YHC group suggests that another factor, such as loss of remote memory, may also contribute to the RA pattern. Loss of remote memory in HD and HIV-D might reflect the diffuse cortical changes that occur in conjunction with subcortical gray and white matter pathology (de la Monte, Vonsattel, & Richardson, 1988;Jackson et al, 1995;Jernigan, Salmon, Butters, & Hesselink, 1991;McArthur, 1994;Navia et al, 1986;Rosas et al, 2002).…”