Evidence map›Paper›PMID 31138892›Full record

ArticleMolecular psychiatry2021

Alzheimer's disease pathology: pathways between central norepinephrine activity, memory, and neuropsychiatric symptoms.

Heidi I L Jacobs, Joost M Riphagen, Inez H G B Ramakers, Frans R J Verhey

Open access · greenAbstract read
PubMed Publisher
In one paragraph

Article in Molecular psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed
6.7field-weighted citation impact, top 2% 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

70 citing papers in PubMed, 107 citations in OpenAlex.

  1. Trial
  2. Review
  3. Article
  4. Stress, stress systems, and Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Observational
  10. Review
  11. Article
  12. Article
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  15. Article
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  18. Article
  19. Noradrenaline Regulation of Brain-Body Communication.Advances in experimental medicine and biology · 2025
    Review
  20. Article

10 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

4 authors at 2 institutions in 2 countries.

Heidi I L Jacobs *Department of Radiology, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA. h.jacobs@maastrichtuniversity.nl.ORCID http://orcid.org/0000-0001-7620-3822
Joost M Riphagen *Faculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, Maastricht, The Netherlands.
Inez H G B RamakersFaculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, Maastricht, The Netherlands.
Frans R J VerheyFaculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, Maastricht, The Netherlands.
Maastricht University · NLHarvard University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The locus coeruleus (LC) supplies norepinephrine to the brain, is one of the first sites of tau deposition in Alzheimer's disease (AD) and modulates a variety of behaviors and cognitive functions. Transgenic mouse models showed that norepinephrine dysregulation after LC lesions exacerbates inflammatory responses, blood-brain barrier leakage (BBB), and cognitive deficits. Here, we investigated relationships between central norepinephrine metabolism, tau and beta-amyloid (Aβ), inflammation, BBB-dysfunction, neuropsychiatric problems, and memory in-vivo in a memory clinic population (total n = 111, 60 subjective cognitive decline, 36 mild cognitively impaired, and 19 AD dementia). Cerebrospinal fluid (CSF) and blood samples were collected and analyzed for 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), CSF/plasma albumin ratio (Q-alb), Aβ, phosphorylated tau, and interleukins. The verbal word learning task and the neuropsychiatric inventory assessed memory functioning and neuropsychiatric symptoms. Structural equation models tested the relationships between all fluid markers, cognition and behavior, corrected for age, education, sex, and clinical dementia rating score. Our results showed that neuropsychiatric symptoms show strong links to both MHPG and p-tau, whereas memory deficits are linked to MHPG via a combination of p-tau and inflammation-driven amyloidosis (30-35% indirect effect contribution). These results suggest that the LC-norepinephrine may be pivotal to understand links between AD pathology and behavioral and cognitive deficits in AD.

Indexed as

Alzheimer DiseaseCognitive DysfunctionAmyloid beta-PeptidesAnimalsBiomarkersMiceNorepinephrinePeptide Fragmentstau ProteinsAmyloid beta-PeptidesBiomarkersNorepinephrinePeptide Fragmentstau Proteins

Identifiers

PMID31138892
OpenAlexW2947261250

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.