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Woulfe J, Kertesz A, Munoz DG. Frontotemporal dementia with ubiquitinated cytoplasmic and intranuclear inclusions

Department of Pathology and Molecular Medicine, McMaster University and The Hamilton Regional Laboratory Medicine Program, Hamilton Health Sciences Corporation, Hamilton, Ontario, Canada
Acta Neuropathologica (Impact Factor: 10.76). 01/2001; 102(1):94-102. DOI: 10.1007/s004010000346

ABSTRACT Dementia of motor neuron disease type (DMND) is a variety of frontotemporal dementia (FTD) which is pathologically defined by characteristic neuronal ubiquitinated, tau- and synuclein-negative intracytoplasmic inclusions. Many cases with this pathology, however, do not have motor neuron disease. In the present study, we document the presence of ubiquitinated neuronal intranuclear inclusions in a sub-population of cases of neuropathologically verified DMND. Immunohistochemical localization of ubiquitin was performed on sections of post-mortem brain from 12 patients with DMND as well as from cases with other neurodegenerative diseases including amyotrophic lateral sclerosis, Parkinson's disease, dementia with Lewy bodies, corticobasal degeneration, progressive supranuclear palsy, and multiple system atrophy. All of the cases of DMND showed ubiquitinated, tau-negative intracytoplasmic inclusions in dentate granule cells and cortical neurons. Of these 12 cases of DMND, 3 also showed neuronal ubiquitinated intranuclear inclusions. In 1 of these cases, CAG repeat expansions in the genes known to harbor these mutations were excluded. Cases with intranuclear inclusions displayed striatal atrophy and reduced brain weight relative to non-inclusion-bearing cases. In addition, patients with intranuclear inclusions tended to have a younger age of onset, a prolonged duration of disease, absence of motor neuron symptoms, and a family history of dementia. Intranuclear inclusions were not identified in the control cases with other neurodegenerative diseases. Ubiquitinated neuronal intranuclear inclusions have not been reported previously in DMND. The presence of ubiquitinated intranuclear inclusions along with striatal atrophy in a subset of cases of DMND may signify the existence of a neuropathologically distinct subset of this unique form of FTD.

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    Dataset: cca-golab
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    • "In the hippocampus, the NCI and NII were counted from sector CA1 to CA2, the short dimension of the contiguous sample field being aligned with the alveus. NCI also occur in the dentate gyrus fascia in FTLD-TDP (Woulfe et el., 2001; Kovari et al., 2004; Mackenzie et al., 2006) and were counted with the sample field aligned with the upper edge of the granule cell layer. The number of NCI and NII were counted in each sample field. "
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    • "Very little pathology was observed to extend into CA3/4 in the cases studied and these areas were not sampled. NCI have been commonly observed in the DG fascia in FTLD-TDP (Mackenzie et al. 2006b; Woulfe et al. 2001; Kovari et al. 2004) and the sample field was aligned with the upper edge of the granule cell layer. The NCI (Fig. 2) are rounded, spicular, or skein-like in shape (Yaguchi et al. 2004; Davidson et al. 2007), while the GI (Figs. 2, 3) morphologically resemble the 'coiled bodies' reported in various tauopathies such as corticobasal degeneration, progressive supranuclear palsy, and argyrophilic grain disease. "
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