Phosphorylated TDP-43 pathology and hippocampal sclerosis in progressive supranuclear palsy View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-07

AUTHORS

Osamu Yokota, Yvonne Davidson, Eileen H. Bigio, Hideki Ishizu, Seishi Terada, Tetsuaki Arai, Masato Hasegawa, Haruhiko Akiyama, Stephen Sikkink, Stuart Pickering-Brown, David M. A. Mann

ABSTRACT

TDP-43 is characteristically accumulated in TDP-43 proteinopathies such as frontotemporal lobar degeneration and motor neurone disease, but is also present in some tauopathies, including Alzheimer's disease, argyrophilic grain disease, and corticobasal degeneration (CBD). However, several studies have suggested that cases of progressive supranuclear palsy (PSP) lack TDP-43 pathology. We have therefore examined limbic regions of the brain in 19 PSP cases, as well as in 12 CBD cases, using phosphorylation-dependent anti-TDP-43 antibodies. We observed TDP-43-positive inclusions in five PSP cases (26%), as well as in two CBD cases (17%). The amygdala and hippocampal dentate gyrus were most frequently affected in PSP. Regional tau burden tended to be higher in TDP-43-positive PSP cases, and a significant correlation between tau and TDP-43 burden was noted in the occipitotemporal gyrus. Hippocampal sclerosis (HS) was found in 3/5 TDP-43-positive PSP cases, but HS was significantly more frequent in TDP-43-positive than TDP-43 negative PSP cases. Dementia was present in 13/19 (58%) of the PSP cases, in 4/5 TDP-43-positive cases, in all 3 TDP-43-positive cases with HS, in 1/2 TDP-43-positive cases without HS, and 7/14 cases lacking both. TDP-43 and tau were frequently colocalized in the amygdala, but not in the hippocampal dentate gyrus. Immunoblotting demonstrated the characteristic (for TDP-43 proteinopathies) 45 and 25 kDa bands and high molecular weight smear in the TDP-43-positive PSP case. These findings suggest that (1) although PSP is nominally a tauopathy, pathological TDP-43 can accumulate in the limbic system in some cases, and (2) TDP-43 pathology may be concurrent with HS. More... »

PAGES

55-66

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00401-010-0702-1

    DOI

    http://dx.doi.org/10.1007/s00401-010-0702-1

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1003885461

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/20512649


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