Distinct TDP-43 inclusion morphologies in frontotemporal lobar degeneration with and without amyotrophic lateral sclerosis

Acta Neuropathologica Communications
Rachel H TanGlenda M Halliday

Abstract

The identification of the TAR DNA-binding protein 43 (TDP-43) as the ubiquitinated cytoplasmic inclusions in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) confirmed that these two diseases share similar mechanisms, likely to be linked to the abnormal hyperphosphorylation, ubiquitination and cleavage of pathological TDP-43. Importantly however, a quantitative analysis of TDP-43 inclusions in predilection cortical regions of FTLD, FTLD-ALS and ALS cases has not been undertaken. The present study set out to assess this and demonstrates that distinct TDP-43 inclusion morphologies exist in the anterior cingulate cortex, but not the motor cortex of FTLD and FTLD-ALS. Specifically, in the anterior cingulate cortex of FTLD cases, significant rounded TDP-43 inclusions and rare circumferential TDP-43 inclusions were identified. In contrast, FTLD-ALS cases revealed significant circumferential TDP-43 inclusions and rare rounded TDP-43 inclusions in the anterior cingulate cortex. Distinct TDP-43 inclusion morphologies in the anterior cingulate cortex of FTLD and FTLD-ALS may be linked to heterogeneity in the ubiquitination of pathological TDP-43 inclusions, with the present study providing evidence to sugg...Continue Reading

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Citations

Dec 24, 2018·Neuropathology and Applied Neurobiology·B BorroniE Buratti
Aug 31, 2018·Acta Neuropathologica Communications·L McGurkN M Bonini
Apr 30, 2019·Frontiers in Neuroscience·Britt A Berning, Adam K Walker
Jul 4, 2020·Acta Neuropathologica Communications·Matthew NolanOlaf Ansorge
Mar 3, 2020·Frontiers in Neuroscience·Yevgeniya A AbramzonRuth Chia
Feb 13, 2018·Expert Opinion on Therapeutic Targets·Emanuele Buratti
Oct 28, 2018·Acta Neuropathologica Communications·Urmi SenguptaRakez Kayed
Jan 28, 2021·Scientific Reports·Smriti AgarwalMatthew C Kiernan
Mar 15, 2019·Journal of the Neurological Sciences·Stéphane MathisGwendal Le Masson

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Methods Mentioned

BETA
ubiquitination

Software Mentioned

SPSS

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