Evidence map›Paper›PMID 32019605›Full record

ArticleActa neuropathologica communications2020

Locus coeruleus pathology in progressive supranuclear palsy, and its relation to disease severity.

Sanne Simone Kaalund, Luca Passamonti, Kieren S J Allinson, Alexander G Murley, Trevor W Robbins, Maria Grazia Spillantini, James B Rowe

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

Article in Acta neuropathologica communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.3field-weighted citation impact, top 9% 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

22 citing papers in PubMed, 37 citations in OpenAlex.

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  10. Ageing-Related Neurodegeneration and Cognitive Decline.International journal of molecular sciences · 2024
    Article
  11. Locus Coeruleus Integrity Is Linked to Response Inhibition Deficits in Parkinson's Disease and Progressive Supranuclear Palsy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023
    Article
  12. Article
  13. Locus Coeruleus Integrity from 7 T MRI Relates to Apathy and Cognition in Parkinsonian Disorders.Movement disorders : official journal of the Movement Disorder Society · 2022
    Article
  14. Locus Coeruleus Shows a Spatial Pattern of Structural Disintegration in Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2022
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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

7 authors at 3 institutions in 3 countries.

Sanne Simone KaalundCambridge University Centre for Parkinson-plus and Department of Clinical Neurosciences, University of Cambridge, Robinson Way, Cambridge, CB2 0SZ, UK. ssk42@medschl.cam.ac.uk.ORCID 0000-0002-8975-1825
Luca PassamontiCambridge University Centre for Parkinson-plus and Department of Clinical Neurosciences, University of Cambridge, Robinson Way, Cambridge, CB2 0SZ, UK.
Kieren S J AllinsonCambridge University Hospitals NHS Foundation Trust and the Cambridge Brain Bank, Cambridge, UK.
Alexander G MurleyCambridge University Centre for Parkinson-plus and Department of Clinical Neurosciences, University of Cambridge, Robinson Way, Cambridge, CB2 0SZ, UK.
Trevor W RobbinsDepartment of Psychology and Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
Maria Grazia SpillantiniCambridge University Centre for Parkinson-plus and Department of Clinical Neurosciences, University of Cambridge, Robinson Way, Cambridge, CB2 0SZ, UK.
James B RoweCambridge University Centre for Parkinson-plus and Department of Clinical Neurosciences, University of Cambridge, Robinson Way, Cambridge, CB2 0SZ, UK.
University of Cambridge · GBCambridge University Hospitals NHS Foundation Trust · GBMRC Cognition and Brain Sciences Unit · GB

Funding

Medical Research Council G0301152Medical Research Council MC_U105597119Medical Research Council MC_UU_00005/12Medical Research Council MR/P01271X/1Medical Research Council SUAG004/051Wellcome TrustWellcome Trust 103838
6 · The paper itself

Abstract

The locus coeruleus is the major source of noradrenaline to the brain and contributes to a wide range of physiological and cognitive functions including arousal, attention, autonomic control, and adaptive behaviour. Neurodegeneration and pathological aggregation of tau protein in the locus coeruleus are early features of progressive supranuclear palsy (PSP). This pathology is proposed to contribute to the clinical expression of disease, including the PSP Richardson's syndrome. We test the hypothesis that tau pathology and neuronal loss are associated with clinical heterogeneity and severity in PSP.We used immunohistochemistry in post mortem tissues from 31 patients with a clinical diagnosis of PSP (22 with Richardson's syndrome) and 6 control cases. We quantified the presence of hyperphosphorylated tau, the number of pigmented cells indicative of noradrenergic neurons, and the percentage of pigmented neurons with tau-positive inclusions. Ante mortem assessment of clinical severity using the PSP rating scale was available within 1.8 (±0.9) years for 23 patients.We found an average 49% reduction of pigmented neurons in PSP patients relative to controls. The loss of pigmented neurons correlated with disease severity, even after adjusting for disease duration and the interval between clinical assessment and death. The degree of neuronal loss was negatively associated with tau-positive inclusions, with an average of 44% of pigmented neurons displaying tau-inclusions.Degeneration and tau pathology in the locus coeruleus are related to clinical heterogeneity of PSP. The noradrenergic deficit in the locus coeruleus is a candidate target for pharmacological treatment. Recent developments in ultra-high field magnetic resonance imaging to quantify in vivo structural integrity of the locus coeruleus may provide biomarkers for noradrenergic experimental medicines studies in PSP.

Indexed as

Adrenergic NeuronsAgedAged, 80 and overFemaleHumansLocus CoeruleusMaleMiddle AgedPhosphorylationSeverity of Illness IndexSupranuclear Palsy, Progressivetau ProteinsMAPT protein, humantau ProteinsFrontotemporal dementiaLocus coeruleusNeurodegenerationNoradrenalinProgressive supranuclear palsyTau

Identifiers

PMID32019605
PMCPMC7001334
OpenAlexW3004510163

What OpenQuestion holds

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LicenceCC BY
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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.