Evidence map›Paper›PMID 26315613›Full record

ArticleAlzheimer's research & therapy2015

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

Sally Hunter, Thais Minett, Tuomo Polvikoski, Elizabeta Mukaetova-Ladinska, Carol Brayne, Cambridge City over-75s Cohort Collaboration

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.9field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 12 citations in OpenAlex.

  1. TDP-43 Proteinopathy and Tauopathy: Do They Have Pathomechanistic Links?International journal of molecular sciences · 2022
    Review
  2. Article
  3. Review
  4. Neuronal Cell Death.Physiological reviews · 2018
    Review
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 2 countries.

Sally HunterDepartment of Public Health and Primary Care, Institute of Public Health, Forvie Site, University of Cambridge School of Clinical Medicine, Box 113 Cambridge Biomedical Campus, Cambridge, CB2 0SP, UK. seh66@medschl.cam.ac.uk.
Thais MinettDepartment of Public Health and Primary Care, Institute of Public Health, Forvie Site, University of Cambridge School of Clinical Medicine, Box 113 Cambridge Biomedical Campus, Cambridge, CB2 0SP, UK. tsm34@medschl.cam.ac.uk.
Tuomo PolvikoskiInstitute of Neuroscience, Henry Wellcome Building for Neuroecology, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK. tuomo.polvikoski@newcastle.ac.uk.
Elizabeta Mukaetova-LadinskaInstitute of Neuroscience, Henry Wellcome Building for Neuroecology, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK. elizabeta.mukaetova-ladinska@newcastle.ac.uk.
Carol BrayneDepartment of Public Health and Primary Care, Institute of Public Health, Forvie Site, University of Cambridge School of Clinical Medicine, Box 113 Cambridge Biomedical Campus, Cambridge, CB2 0SP, UK. cb105@medschl.cam.ac.uk.
Cambridge City over-75s Cohort Collaboration
Newcastle University · GBUniversity of Cambridge · GBCambridge School · PT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionAlzheimer'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.

methodsWe 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.

resultsHippocampal 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.

conclusionsCurrent 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.

Indexed as

Aged, 80 and overDementiaFemaleHippocampusHumansImmunohistochemistryLogistic ModelsLongitudinal StudiesMaleNerve DegenerationNeurofibrillary TanglesNeuronsSeverity of Illness Indextau ProteinsMAPT protein, humantau Proteins

Identifiers

PMID26315613
PMCPMC4551529
OpenAlexW1901198361

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.