A pathogenic progranulin mutation and C9orf72 repeat expansion in a family with frontotemporal dementia.
Bottom Line: Brain imaging from available cases showed a symmetrical pattern of atrophy particularly affecting the frontal and temporal lobes.Pathologically two cases were classified as FTLD-TDP type A with TDP-43 positive inclusions, with additional p62-positive 'star-like' inclusions found in the hippocampal formation and cerebellum.However the driving force of the pathological process may be either pathogenic mutation or a combination of both converging on a singular mechanism.
Affiliation: Queen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.Show MeSH
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Mentions: In case 2.1 neurofibrillary tangles (NFTs) and neuropil threads (NTs) were found in the hippocampus, entorhinal and transentorhinal cortices. TDP-43 positive NCIs were observed in the granule cells of the dentate fascia but these were outnumbered by numerous p62-positive ‘star-like’ inclusions (Figure 4). The majority of the p62-positive inclusions were also immunostained with ubiquilin2 (Figure 4), although there were still inclusions that were only positively stained with p62. The p62-positive ‘star-like’ inclusions were also found in the CA4 subregion, which was negative for TDP-43. Case 2.2 showed a similar distribution of TDP-43 and p62 inclusions as that observed in cases 2.1; however no additional pathology was evident.
Affiliation: Queen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.