Evidence map›Paper›PMID 31023342›Full record

ArticleActa neuropathologica communications2019

Hippocampal CA2 Lewy pathology is associated with cholinergic degeneration in Parkinson's disease with cognitive decline.

Alan King Lun Liu, Tsz Wing Chau, Ernest Junwei Lim, Idil Ahmed, Raymond Chuen-Chung Chang, Michail E Kalaitzakis, Manuel B Graeber, Steve M Gentleman, Ronald K B Pearce

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

Article in Acta neuropathologica communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
4.7field-weighted citation impact, top 5% 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

34 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. The Aggregation ofBiomedicines · 2024
    Article
  5. Observational
  6. Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Review
  12. Advances in the study of cholinergic circuits in the central nervous system.Annals of clinical and translational neurology · 2023
    Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Morphological basis of Parkinson disease-associated cognitive impairment: an update.Journal of neural transmission (Vienna, Austria : 1996) · 2022
    Review
  20. 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

9 authors at 4 institutions in 3 countries.

Alan King Lun LiuNeuropathology Unit, Division of Brain Sciences, Department of Medicine, Imperial College London, 4/F, Burlington Danes Building, Du Cane Road, London, W12 0NN, UK. alan.kl.liu@doctors.org.uk.ORCID 0000-0001-6109-1338
Tsz Wing ChauNeuropathology Unit, Division of Brain Sciences, Department of Medicine, Imperial College London, 4/F, Burlington Danes Building, Du Cane Road, London, W12 0NN, UK.
Ernest Junwei LimNeuropathology Unit, Division of Brain Sciences, Department of Medicine, Imperial College London, 4/F, Burlington Danes Building, Du Cane Road, London, W12 0NN, UK.
Idil AhmedNeuropathology Unit, Division of Brain Sciences, Department of Medicine, Imperial College London, 4/F, Burlington Danes Building, Du Cane Road, London, W12 0NN, UK.
Raymond Chuen-Chung ChangLaboratory of Neurodegenerative Diseases, School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR.
Michail E KalaitzakisNeuropathology Unit, Division of Brain Sciences, Department of Medicine, Imperial College London, 4/F, Burlington Danes Building, Du Cane Road, London, W12 0NN, UK.
Manuel B GraeberBrain and Mind Centre, Bosch Institute, Discipline of Anatomy and Embryology, and Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, 94 Mallett Street, Camperdown, NSW, 2050, Australia.
Steve M GentlemanNeuropathology Unit, Division of Brain Sciences, Department of Medicine, Imperial College London, 4/F, Burlington Danes Building, Du Cane Road, London, W12 0NN, UK.
Ronald K B PearceNeuropathology Unit, Division of Brain Sciences, Department of Medicine, Imperial College London, 4/F, Burlington Danes Building, Du Cane Road, London, W12 0NN, UK.
Imperial College London · GBKing's College London · GBThe University of Sydney · AUUniversity of Hong Kong · HK

Funding

THE APOE-APP AXIS IN ALZHEIMER PATHOGENESISP01AG012411 · NIA · UNIV OF ARKANSAS FOR MED SCIS · PI GRIFFIN, SUE TILTON · 1995 to 2020
$25.0M
NIA NIH HHS P01 AG012411
6 · The paper itself

Abstract

Although the precise neuropathological substrates of cognitive decline in Parkinson's disease (PD) remain elusive, it has long been regarded that pathology in the CA2 hippocampal subfield is characteristic of Lewy body dementias, including dementia in PD (PDD). Early non-human primate tracer studies demonstrated connections from the nucleus of the vertical limb of the diagonal band of Broca (nvlDBB, Ch2) to the hippocampus. However, the relationship between Lewy pathology of the CA2 subfield and cholinergic fibres has not been explored. Therefore, in this study, we investigated the burden of pathology in the CA2 subsector of PD cases with varying degrees of cognitive impairment and correlated this with the extent of septohippocampal cholinergic deficit. Hippocampal sections from 67 PD, 34 PD with mild cognitive impairment and 96 PDD cases were immunostained for tau and alpha-synuclein, and the respective pathology burden was assessed semi-quantitatively. In a subset of cases, the degree of CA2 cholinergic depletion was quantified using confocal microscopy and correlated with cholinergic neuronal loss in Ch2. We found that only cases with dementia have a significantly greater Lewy pathology, whereas cholinergic fibre depletion was evident in cases with mild cognitive impairment and this was significantly correlated with loss of cholinergic neurons in Ch2. In addition, multiple antigen immunofluorescence demonstrated colocalisation between cholinergic fibres and alpha-synuclein but not tau pathology. Such specific Lewy pathology targeting the cholinergic system within the CA2 subfield may contribute to the unique memory retrieval deficit seen in patients with Lewy body disorders, as distinct from the memory storage deficit seen in Alzheimer's disease.

Indexed as

AgedAged, 80 and overalpha-SynucleinCA2 Region, HippocampalCholinergic NeuronsCognitive DysfunctionFemaleHumansLewy BodiesMaleParkinson Diseasetau Proteinsalpha-SynucleinMAPT protein, humantau ProteinsAlzheimer’s diseaseCA2Cholinergic systemDiagonal band of BrocaHippocampusParkinson’s disease

Identifiers

PMID31023342
PMCPMC6485180
OpenAlexW2946666527

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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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.