期刊
BRAIN
卷 129, 期 -, 页码 3081-3090出版社
OXFORD UNIV PRESS
DOI: 10.1093/brain/awl271
关键词
frontotemporal dementia; frontotemporal lobar degeneration; ubiquitin; progranulin; neuronal intranuclear inclusions
资金
- Medical Research Council [G0400356] Funding Source: researchfish
- MRC [G0400356] Funding Source: UKRI
- Medical Research Council [G0400356] Funding Source: Medline
- NIA NIH HHS [P50 AG16574, R01 AG026251, P01 AG017216] Funding Source: Medline
The most common pathology in frontotemporal dementia (FTD) is tau-negative, ubiquitin-immunoreactive (ub-ir) neuronal inclusions (FTLD-U). Recently, we identified mutations in the progranulin (PGRN) gene as the cause of autosomal dominant FTLD-U linked to chromosome 17. Here, we describe the neuropathology in 13 patients from 6 different families, each with FTD caused by a different PGRN mutation. The most consistent feature was the presence of ub-ir lentiform neuronal intranuclear inclusions (NII) in the neocortex and striatum. In addition, the neocortex showed moderate-to-severe superficial laminar spongiosis, chronic degenerative changes, ub-ir neurites and well-defined ub-ir neuronal cytoplasmic inclusions (NCI). In the striatum, there were numerous ub-ir neurites. NCI in the hippocampus usually had a granular appearance. In contrast, familial FTLD-U cases without PGRN mutations had no NII, less severe neocortical and striatal pathology and hippocampal NCI that were more often solid. Eight cases in which genetic analysis was not available also had NII and an overall pathology similar to those with proven mutations. None of our cases of FTLD-U without NII showed the same pattern of pathology as those with mutations. These findings suggest that FTD caused by PGRN mutations has a recognizable pathology with the most characteristic feature being ub-ir NII.
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