Wharton, S.B., Minett, T., Drew, D. et al. (5 more authors) (2016) Epidemiological pathology of Tau in the ageing brain: application of staging for neuropil threads (BrainNet Europe protocol) to the MRC cognitive function and ageing brain study. Acta Neuropathol Communications, 4. 11. ISSN 2051-5960
Abstract
INTRODUCTION: Deposition of abnormally phosphorylated tau (phospho-tau) occurs in Alzheimer'sdisease but also with brain ageing. The Braak staging scheme focused on neurofibrillary tangles, butabundant p-tau is also present in neuropil threads, and a recent scheme has been proposed by theBrainNet Europe consortium for staging tau pathology based on neuropil threads. We determined therelationship of threads to tangles, and the value of staging for threads in an unselected population-representative ageing brain cohort. We also determined the prevalence of astroglial tau pathologies, and their relationship to neuronal tau. Phospho-tau pathology was determined by immunohistochemistry (AT8 antibody) in the MRC-CFAS neuropathology cohort. Neuropil threads were staged using the BrainNet Europe protocol for tau pathology, and compared with Braak tangle stages. Astroglial tau pathology was assessed in neo-cortical, mesial temporal and subcortical areas. RESULTS: Cases conformed well to the hierarchical neuropil threads staging of the BrainNet Europe protocol and correlated strongly with Braak staging (r=0.84, p < 0.001). Based on the areas under the receiver operator curves (AUC), incorporating either threads or tangle staging significantly improved dementia case identification to a similar degree over age alone (Braak stage X (2)(1)=10.1, p=0.002; BNE stage X (2)(1)=9.7, p=0.002). Thorn-shaped astrocytes, present in 40 % of cases, were most common in mesial temporal lobe, then brainstem, and were associated with subpial tau-positive neurites (mesial temporal: X (2)(1)=61.3, p < 0.001; brainstem: X (2)(1)=47.9, p < 0.001). Adding thorn astrocytes did not improve dementia prediction (AUC: X (2)(1)=0.77, p=0.381), but there was a weak relationship between numbers of areas involved and staging for threads or tangles (r=0.17, p=0.023). Neuropil threads develop hierarchically in parallel with neurofibrillary tangles. CONCLUSIONS: The BrainNet Europe staging protocol is straightforward to apply, and offers similar predictive value for dementia to Braak tangle staging. Astroglial tauopathy, particularly thorn shaped astrocyte formation, does not relate to dementia status, but the association with phospho-tau neurites may suggest a pathogenic relationship to neuronal tau pathology.
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Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 Wharton et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
Keywords: | Alzheimer’s disease; Brain ageing; Tauopathy; Neuropil threads; Staging schemes; Thorn-shaped astrocytes; Braak Stage; BrainNet Europe |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Neuroscience (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number MEDICAL RESEARCH COUNCIL G0900582/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 11 Apr 2016 11:50 |
Last Modified: | 03 Apr 2019 14:52 |
Published Version: | http://dx.doi.org/10.1186/s40478-016-0275-x |
Status: | Published |
Publisher: | BioMed Central |
Refereed: | Yes |
Identification Number: | 10.1186/s40478-016-0275-x |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:95339 |
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