Evidence map›Paper›PMID 34219717›Full record

ReviewJournal of Alzheimer's disease : JAD2021

The Locus Coeruleus in Aging and Alzheimer's Disease: A Postmortem and Brain Imaging Review.

Rebecca Beardmore, Ruihua Hou, Angela Darekar, Clive Holmes, Delphine Boche

Open access · hybridAbstract readReview
In one paragraph

Review in Journal of Alzheimer's disease : JAD, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
9.7field-weighted citation impact, top 1% 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

75 citing papers in PubMed, 114 citations in OpenAlex.

  1. Trial
  2. Article
  3. Vulnerability of locus coeruleus connections to aging and Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Attenuated pupillary response during visual search in preclinical Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Review
  20. Article

15 more citing papers are in PubMed but not listed here.

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

5 authors at 3 institutions in 1 country.

Rebecca BeardmoreClinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Ruihua HouClinical and Experimental Sciences, Department of Psychiatry, Faculty of Medicine, University of Southampton, Southampton, UK.
Angela DarekarDepartment of Medical Physics, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Clive HolmesClinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Delphine BocheClinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Moorgreen Hospital · GBUniversity of Southampton · GBUniversity Hospital Southampton NHS Foundation Trust · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The locus coeruleus (LC), a tiny nucleus in the brainstem and the principal site of noradrenaline synthesis, has a major role in regulating autonomic function, arousal, attention, and neuroinflammation. LC dysfunction has been linked to a range of disorders; however particular interest is given to the role it plays in Alzheimer's disease (AD). The LC undergoes significant neuronal loss in AD, thought to occur early in the disease process. While neuronal loss in the LC has also been suggested to occur in aging, this relationship is less clear as the findings have been contradictory. LC density has been suggested to be indicative of cognitive reserve and the evidence for these claims will be discussed. Recent imaging techniques allowing visualization of the LC in vivo using neuromelanin-sensitive MRI are developing our understanding of the role of LC in aging and AD. Tau pathology within the LC is evident at an early age in most individuals; however, the relationship between tau accumulation and neuronal loss and why some individuals then develop AD is not understood. Neuromelanin pigment accumulates within LC cells with age and is proposed to be toxic and inflammatory when released into the extracellular environment. This review will explore our current knowledge of the LC changes in both aging and AD from postmortem, imaging, and experimental studies. We will discuss the reasons behind the susceptibility of the LC to neuronal loss, with a focus on the role of extracellular neuromelanin and neuroinflammation caused by the dysfunction of the LC-noradrenaline pathway.

Indexed as

Magnetic Resonance ImagingAgingAlzheimer DiseaseAnimalsAutopsyBrain StemHumansLocus CoeruleusMelaninsMiceNorepinephrineRatstau ProteinsMelaninsneuromelaninNorepinephrinetau ProteinsAgingAlzheimer’s diseasehumanlocus coeruleusmagnetic resonance imagingneuromelanin

Identifiers

PMID34219717
PMCPMC8461706
OpenAlexW3182932762

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

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 Socratic graph.