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Re-examining tau-immunoreactive pathology in the population: granulovacuolar degeneration and neurofibrillary tangles.

Published version
Peer-reviewed

Repository DOI


Type

Article

Change log

Authors

Soares Cianciarullo Minett, Thais  ORCID logo  https://orcid.org/0000-0002-3232-9455
Polvikoski, Tuomo 
Mukaetova-Ladinska, Elizabeta 

Abstract

INTRODUCTION: Alzheimer's disease (AD) is associated with neurofibrillary pathology, including neurofibrillary tangles (NFT), neuritic plaques (NP) and neuropil threads containing aggregated microtubule associated protein tau. Aggregated tau is also associated with granulovacuolar degeneration (GVD). The relationships between tau, GVD, NFT and dementia are unclear. METHODS: We assessed hippocampal (CA1) tau-immunoreactive GVD and NFT pathology in brain donations from the population-representative Cambridge City over 75s Cohort (CC75C) using the CERAD protocol and a modified protocol that included a morphological characterisation of tau-immunoreactive deposits within neurons as NFTs or as GVD. Associations between GVD, NFT and dementia were investigated. RESULTS: Hippocampal pyramidal neurons affected with either NFT or GVD are common in the older population. Some tau-immunoreactive deposits resemble ghost GVD neurons. Tau immunoreactivity identified GVD in 95% cases rated as none with haematoxylin and eosin staining. Both severe NFT (odds ratio (OR) 7.33, 95% confidence interval (CI) 2.01; 26.80, p = 0.003) and severe GVD (OR 7.48, 95% (CI) 1.54; 36.24, p = 0.012) were associated with dementia status. Increasing NFT (OR 2.47 95% (CI) 1.45; 4.22, p = 0.001) and GVD (OR 2.12 95% (CI) 1.23; 3.64, p = 0.007) severities are associated with increasing dementia severity. However, when the analyses were controlled for other neuropathologies (NFT, NP, Tar-DNA binding Protein-43 and amyloid deposits), the associations between GVD and dementia lost significance. CONCLUSIONS: Current neuropathological assessments do not adequately evaluate the presence and severity of the GVD pathology and its contribution to dementia remains unclear. We recommend that protocols to assess GVD should be developed for routine use and that tau, in a non-PHF associated conformation, is reliably associated with GVD.

Description

Keywords

Aged, 80 and over, Dementia, Female, Hippocampus, Humans, Immunohistochemistry, Logistic Models, Longitudinal Studies, Male, Nerve Degeneration, Neurofibrillary Tangles, Neurons, Severity of Illness Index, tau Proteins

Journal Title

Alzheimers Res Ther

Conference Name

Journal ISSN

1758-9193
1758-9193

Volume Title

7

Publisher

Springer Science and Business Media LLC
Sponsorship
CC75C is a member study of the Cambridgeshire and Peterborough Collaboration for Leadership in Applied Health Research and Care (CLAHRC). The Cambridge Brain Bank Laboratory (which processed all CC75C cases) is supported by the National Institute for Health Research, Cambridge BioMedical Research Centre. EM-L is supported by Alzheimer’s Society (London, UK).