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Frontotemporal lobar degeneration with ubiquitinated tau‐negative inclusions and additional α‐synuclein pathology but also unusual cerebellar ubiquitinated p62‐positive, TDP‐43‐negative inclusions
Author(s) -
King Andrew,
AlSarraj Safa,
Shaw Christopher
Publication year - 2009
Publication title -
neuropathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 61
eISSN - 1440-1789
pISSN - 0919-6544
DOI - 10.1111/j.1440-1789.2008.00966.x
Subject(s) - frontotemporal lobar degeneration , ubiquitin , tauopathy , pathology , frontotemporal dementia , neuropathology , biology , pathological , cerebellum , mutation , neurodegeneration , medicine , genetics , gene , dementia , neuroscience , disease
Mutations in the progranulin ( PGRN ) gene on chromosome 17 have been shown to be responsible for one non‐tauopathy subtype of familial frontotemporal lobar degeneration – frontotemporal lobar degeneration with ubiquitinated, tau‐negative inclusions (FTLD‐U). Such cases have pathological similarities to sporadic cases with neuronal inclusions positive for ubiquitin, the ubiquitin binding protein, p62 and the newly recognised protein TDP‐43 but negative for hyperphosphorylated (HP) tau. There has been a recent report on two families with a novel progranulin mutation where the neuropathology showed not only TDP‐43 neuronal positivity but separate tau and/or α‐synuclein pathology. We describe an unusual case with some family history but no mutation in the progranulin gene. The pathological features were typical for FTLD‐U but with additional significant α‐synuclein pathology, and unusual ubiquitin‐positive, p62‐positive, TDP‐43‐negative inclusions in the cerebellum. This case may represent a further pathological phenotype for familial FTLD‐U. It also highlights the need for further investigations on the ubiquitin binding protein p62 as a marker in FTLD‐U. It is certainly possible that the presence or absence of these ubiquitinated p62‐positive yet TDP‐43‐negative cerebellar inclusions may act as a useful correlative factor in the future.