Frontotemporal lobar degeneration with ubiquitinated tau-negative inclusions and additional alpha-synuclein pathology but also unusual cerebellar ubiquitinated p62-positive, TDP-43-negative inclusions.

Neuropathology : Official Journal of the Japanese Society of Neuropathology
Andrew KingChristopher E Shaw

Abstract

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 alpha-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 alpha-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 ubiquit...Continue Reading

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Citations

Mar 28, 2013·DNA and Cell Biology·Xiaolong LinZuo Wang
Apr 20, 2010·Human Molecular Genetics·Clotilde Lagier-TourenneDon W Cleveland
Jun 19, 2012·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Eileen H BigioM-Marsel Mesulam
Jul 6, 2010·Neurobiology of Disease·Cyntia Curcio-MorelliSusan A Slaugenhaupt
Apr 7, 2011·Movement Disorders : Official Journal of the Movement Disorder Society·Lucilla ParnettiOmar El-Agnaf
Mar 4, 2015·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Johnathan Cooper-KnockPamela J Shaw
Jul 31, 2013·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration·Tino Prell, Julian Grosskreutz
Nov 18, 2021·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration

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