Evidence map›Paper›PMID 37990275›Full record

ArticleJournal of neuroinflammation2023

Microglial activation, tau and amyloid deposition in TREM2 p.R47H carriers and mild cognitive impairment patients: a multi-modal/multi-tracer PET/MRI imaging study with influenza vaccine immune challenge.

Oliver Cousins, Julia J Schubert, Avinash Chandra, Mattia Veronese, Polena Valkimadi, Byron Creese, Zunera Khan, Ryan Arathimos, Adam Hampshire, Ivana Rosenzweig and 12 more

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

Article in Journal of neuroinflammation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

8 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Roles of TREM2 in Alzheimer's disease.Translational neurodegeneration · 2025
    Review
  6. Review
  7. Review
  8. Review
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

22 authors at 7 institutions in 2 countries.

Oliver CousinsInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9RT, UK.
Julia J SchubertInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9RT, UK.
Avinash ChandraInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9RT, UK.
Mattia VeroneseInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9RT, UK.
Polena ValkimadiInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9RT, UK.
Byron CreeseCollege of Medicine and Health, University of Exeter, Exeter, EX1 2HZ, UK.
Zunera KhanInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9RT, UK.
Ryan ArathimosInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9RT, UK.
Adam HampshireFaculty of Medicine, Imperial College London, London, SW7 2AZ, UK.
Ivana RosenzweigInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9RT, UK.
Clive BallardCollege of Medicine and Health, University of Exeter, Exeter, EX1 2HZ, UK.
Anne CorbettCollege of Medicine and Health, University of Exeter, Exeter, EX1 2HZ, UK.
Dag AaslandInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9RT, UK.
Latha VelayudhanInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9RT, UK.
Michael O'NeillEli Lilly and Company, Basingstoke, RG21 4FA, UK.
David CollierEli Lilly and Company, Basingstoke, RG21 4FA, UK.
Ramla AwaisCentre for Radiopharmaceutical Chemistry, University College London, London, WC1E 6BS, UK.
Kerstin SanderCentre for Radiopharmaceutical Chemistry, University College London, London, WC1E 6BS, UK.
Erik ÅrstadCentre for Radiopharmaceutical Chemistry, University College London, London, WC1E 6BS, UK.
Oliver HowesInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9RT, UK.
Federico TurkheimerInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9RT, UK.
Angela HodgesInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9RT, UK. Angela.k.hodges@kcl.ac.uk.
King's College London · GBUniversity College London · GBEli Lilly (United Kingdom) · GBUniversity of Exeter · GBBrunel University of London · GBImperial College London · GBUniversity of Padua · IT

Funding

Innovative Medicines Initiative 2 Joint Undertaking No 115976MRC Proximity to Discovery: Industry Engagement Fund (External Collaboration, Innovation and Entrepreneurism: Translational Medicine in Exeter 2 (EXCITEME2) ref. MC_PC_17189) MR/N015746/1
6 · The paper itself

Abstract

backgroundMicroglia are increasingly understood to play an important role in the pathogenesis of Alzheimer's disease. The rs75932628 (p.R47H) TREM2 variant is a well-established risk factor for Alzheimer's disease. TREM2 is a microglial cell surface receptor. In this multi-modal/multi-tracer PET/MRI study we investigated the effect of TREM2 p.R47H carrier status on microglial activation, tau and amyloid deposition, brain structure and cognitive profile.

methodsWe compared TREM2 p.R47H carriers (n = 8; median age = 62.3) and participants with mild cognitive impairment (n = 8; median age = 70.7). Participants underwent two [

resultsCompared to participants with mild cognitive impairment, TREM2 carriers had lower TSPO signal in Braak II (P = 0.04) and Braak III (P = 0.046) regions, despite having a similar burden of tau and amyloid. There were trends to suggest reduced microglial activation following influenza vaccine in TREM2 carriers. Tau deposition in the Braak VI region was higher in TREM2 carriers (P = 0.04). Furthermore, compared to healthy controls TREM2 carriers had smaller caudate (P = 0.02), total brain (P = 0.049) and white matter volumes (P = 0.02); and neuropsychological assessment revealed worse ADAS-Cog13 (P = 0.03) and Delayed Matching to Sample (P = 0.007) scores.

conclusionsTREM2 p.R47H carriers had reduced levels of microglial activation in brain regions affected early in the Alzheimer's disease course and differences in brain structure and cognition. Changes in microglial response may underlie the increased Alzheimer's disease risk in TREM2 p.R47H carriers. Future therapeutic agents in Alzheimer's disease should aim to enhance protective microglial actions.

Indexed as

Alzheimer DiseaseCognitive DysfunctionInfluenza VaccinesAgedAmyloidAmyloid beta-PeptidesHumansMagnetic Resonance ImagingMembrane GlycoproteinsMicrogliaMiddle AgedPositron-Emission TomographyReceptors, GABAReceptors, Immunologictau ProteinsAmyloidAmyloid beta-PeptidesInfluenza VaccinesMembrane GlycoproteinsReceptors, GABAReceptors, Immunologictau ProteinsTREM2 protein, humanTSPO protein, humanAlzheimer’s diseaseAV1451DPA714FlorbetapirMicrogliaNeuroinflammationPETTREM2TSPO

Identifiers

PMID37990275
PMCPMC10664604
OpenAlexW4388856397

What OpenQuestion holds

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LicenceCC BY
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.