Morphological differences of intraneuronal ubiquitin‐positive inclusions in the dentate gyrus and parahippocampal gyrus of motor neuron disease with dementia

Abstract

Semiquantitative morphological analysis of cerebral intraneuronal ubiquitin-positive tau-negative inclusions, a pathologic marker for motor neuron disease with dementia (MND-D), was performed in the dentate gyrus and parahippocampal gyrus of 20 clinicopathologically confirmed patients with MND-D. The forms of the inclusions were tentatively classified into three types: (i) C-type, consisting of relatively large and intensely stained crescent or circular structures; (ii) L-type, showing fine linear structures around the nuclei; and (iii) G-type, showing faintly stained granular structures. The frequencies of the C-type, L-type and G-type was 0.5-9.3%,0.2-6.5% and 0-6.6% of dentate granule cells, respectively. In contrast to the dentate gyrus, almost all inclusions showed either the C-type or L-type form in the parahippocampal gyrus. A positive correlation was noted only between incidences of C-type inclusion of the dentate gyrus and that of the parahippocampal gyrus (r = 0.69, P < 0.05). The morphological differences of the inclusions probably reflect different stages of their formation.

Cortical degeneration in frontotemporal lobar degeneration with TDP-43 proteinopathy caused byprogranulingene mutation

“…The NCI were rounded, spicular, or skein-like [15,17,27], while the GI resembled similar inclusions reported in the tauopathies [28][29][30][31][32] The NII were lenticular, spindle-shaped, or circular [16,17] and the DN often long and contorted in shape [17,33]. Neurons had a larger shape, nonspherical outline and contained at least some cytoplasm [34], while glial cells comprised small spherical or asymmetrical nuclei without cytoplasm.…”

Different molecular pathologies result in similar spatial patterns of cellular inclusions in neurodegenerative disease: a comparative study of eight disorders

“…NCI also exhibit different morphologies, but the majority are either flame-shaped, e.g., NFT in AD, CBD, and PSP or globose, e.g., PiD, DLB, and NIFID. In contrast, a variety of inclusion morphologies are often present in FTLD-TDP including rounded, spicular, or skein-like inclusions (Davidson et al 2007; Yaguchi et al 2004). …”

Comparative quantitative study of ‘signature’ pathological lesions in the hippocampus and adjacent gyri of 12 neurodegenerative disorders

“…HC pathways in PiD may be particularly vulnerable to tau pathology (Garcia-Sierra et al 2000), but occasional a-and b-synuclein-immunoreactive PB have also been observed in the DG in this disorder (Mori et al 2002). A similar distribution of pathology is present in sporadic FTLD-TDP, although to a lesser extent (Yang and Schmitt 2001;Woulfe et al 2001;Rosso et al 2001;Arai et al 2003, Kovari et al 2004Yaguchi et al 2004;Mackenzie et al 2006), including cases with hippocampal sclerosis (HS) (Probst et al 2007), the latter often exhibiting neuronal loss in the subiculum and CA1 (Josephs and Dickson 2007). TDP-43 immunoreactive dendrites have also been observed in HC neurons in the form of RNA granules co-localized with the post-synaptic protein PDS-95 (Wang et al 2008).…”