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Pathological tau deposition in Motor Neurone Disease and frontotemporal lobar degeneration associated with TDP-43 proteinopathy

Overview of attention for article published in Acta Neuropathologica Communications, March 2016
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (78th percentile)
  • Average Attention Score compared to outputs of the same age and source

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1 news outlet

Citations

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18 Dimensions

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40 Mendeley
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Title
Pathological tau deposition in Motor Neurone Disease and frontotemporal lobar degeneration associated with TDP-43 proteinopathy
Published in
Acta Neuropathologica Communications, March 2016
DOI 10.1186/s40478-016-0301-z
Pubmed ID
Authors

Roya Behrouzi, Xiawei Liu, Dongyue Wu, Andrew C. Robinson, Sayuri Tanaguchi-Watanabe, Sara Rollinson, Jing Shi, Jinzhou Tian, Hisham H. M. Hamdalla, John Ealing, Anna Richardson, Matthew Jones, Stuart Pickering-Brown, Yvonne S. Davidson, Michael J. Strong, Masato Hasegawa, Julie S. Snowden, David M. A. Mann

Abstract

It has been suggested that patients with motor neurone disease (MND) and those with MND combined with behavioural variant frontotemporal dementia (bvFTD) (ie FTD + MND) or with FTD alone might exist on a continuum based on commonalities of neuropathology and/or genetic risk. Moreover, it has been reported that both a neuronal and a glial cell tauopathy can accompany the TDP-43 proteinopathy in patients with motor neurone disease (MND) with cognitive changes, and that the tauopathy may be fundamental to disease pathogenesis and clinical phenotype. In the present study, we sought to substantiate these latter findings, and test this concept of a pathological continuum, in a consecutive series of 41 patients with MND, 16 with FTD + MND and 23 with FTD without MND. Paraffin sections of frontal, entorhinal, temporal and occipital cortex and hippocampus were immunostained for tau pathology using anti-tau antibodies, AT8, pThr(175) and pThr(217), and for amyloid β protein (Aβ) using 4G8 antibody. Twenty four (59 %) patients with MND, 7 (44 %) patients with FTD + MND and 10 (43 %) patients with FTD showed 'significant' tau pathology (ie more than just an isolated neurofibrillary tangle or a few neuropil threads in one or more brain regions examined). In most instances, this bore the histological characteristics of an Alzheimer's disease process involving entorhinal cortex, hippocampus, temporal cortex, frontal cortex and occipital cortex in decreasing frequency, accompanied by a deposition of Aβ up to Thal phase 3, though 2 patients with MND, and 1 with FTD did show tau pathology beyond Braak stage III. Four other patients with MND showed novel neuronal tau pathology, within the frontal cortex alone, specifically detected by pThr(175) antibody, which was characterised by a fine granular or more clumped aggregation of tau without neurofibrillary tangles or neuropil threads. However, none of these 4 patients had clinically evident cognitive disorder, and this type of tau pathology was not seen in any of the FTD + MND or FTD patients. Finally, two patients, one with MND and one with FTD, showed a tau pathology consistent with Argyrophilic Grain Disease (AGD). Western blotting and use of 3- and 4-repeat tau antibodies confirmed the histological interpretation of Alzheimer's disease type pathology in all instances except for those patients with accompanying AGD where a banding pattern on western blot, and immunohistochemistry, confirmed 4-repeat tauopathy. In all 3 patient groups, amyloid pathology was more likely to be present in patients dying after 65 years of age, and in the presence of APOE ε4 allele. We conclude that tau pathological changes are equally common amongst patients with MND, FTD + MND and FTD though, in most instances, these are limited in extent. In patients with MND, when cognitive impairment is present this is most likely due to an accompanying/evolving (coincidental) Alzheimer's disease process or, as in a single case, Dementia with Lewy bodies, within the cerebral cortex rather than as a result of TDP-43 proteinopathy. Conversely, in FTD and FTD + MND dementia is more likely to be associated with TDP-43 proteinopathy than tau. Hence, present study shows no progression in severity of (tau) pathology from MND through FTD + MND to FTD, and does not support the concept of these conditions forming a continuum of clinical or pathological change.

Mendeley readers

The data shown below were compiled from readership statistics for 40 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 3%
Philippines 1 3%
Belgium 1 3%
Unknown 37 93%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 8 20%
Student > Master 8 20%
Unspecified 5 13%
Student > Bachelor 4 10%
Researcher 4 10%
Other 11 28%
Readers by discipline Count As %
Agricultural and Biological Sciences 9 23%
Neuroscience 9 23%
Unspecified 6 15%
Biochemistry, Genetics and Molecular Biology 5 13%
Medicine and Dentistry 4 10%
Other 7 18%

Attention Score in Context

This research output has an Altmetric Attention Score of 7. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 April 2016.
All research outputs
#1,027,026
of 7,520,778 outputs
Outputs from Acta Neuropathologica Communications
#126
of 352 outputs
Outputs of similar age
#55,089
of 272,413 outputs
Outputs of similar age from Acta Neuropathologica Communications
#18
of 34 outputs
Altmetric has tracked 7,520,778 research outputs across all sources so far. Compared to these this one has done well and is in the 85th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 352 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.2. This one has gotten more attention than average, scoring higher than 56% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 272,413 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 78% of its contemporaries.
We're also able to compare this research output to 34 others from the same source and published within six weeks on either side of this one. This one is in the 38th percentile – i.e., 38% of its contemporaries scored the same or lower than it.