Evidence map›Paper›PMID 40329311›Full record

ArticleAlzheimer's research & therapy2025

Assessment of the relationship between synaptic density and metabotropic glutamate receptors in early Alzheimer's disease: a multi-tracer PET study.

Elaheh Salardini, Ryan S O'Dell, Em Tchorz, Nabeel B Nabulsi, Yiyun Huang, Richard E Carson, Christopher H van Dyck, Adam P Mecca

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Trajectories of late-life depression: insights from molecular imaging.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Review
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Elaheh SalardiniAlzheimer's Disease Research Unit, Yale University School of Medicine, One Church Street, 8 Floor, New Haven, CT, 06510, USA.
Ryan S O'DellAlzheimer's Disease Research Unit, Yale University School of Medicine, One Church Street, 8 Floor, New Haven, CT, 06510, USA.
Em TchorzAlzheimer's Disease Research Unit, Yale University School of Medicine, One Church Street, 8 Floor, New Haven, CT, 06510, USA.
Nabeel B NabulsiDepartment of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA.
Yiyun HuangDepartment of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA.
Richard E CarsonDepartment of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA.
Christopher H van DyckAlzheimer's Disease Research Unit, Yale University School of Medicine, One Church Street, 8 Floor, New Haven, CT, 06510, USA.
Adam P MeccaAlzheimer's Disease Research Unit, Yale University School of Medicine, One Church Street, 8 Floor, New Haven, CT, 06510, USA. adam.mecca@yale.edu.

Funding

PET Imaging of Synaptic Density in Alzheimers DiseaseR01AG052560 · NIA · YALE UNIVERSITY · PI CARSON, RICHARD E., VAN DYCK, CHRISTOPHER H · 2017 to 2020
$3.2M
Investigation of molecular changes in mGluR5 and SV2A to study synaptic alterations in Alzheimer's disease using PET.K23AG057794 · NIA · YALE UNIVERSITY · PI MECCA, ADAM PETER · 2018 to 2022
$977k
NIA NIH HHS K23 AG057794NIA NIH HHS K23AG057794NIA NIH HHS R01 AG052560NIA NIH HHS R01AG052560
6 · The paper itself

Abstract

backgroundThe pathological effects of amyloid β oligomers (Aβo) may be mediated through the metabotropic glutamate receptor subtype 5 (mGluR5), leading to synaptic loss in Alzheimer's disease (AD). Positron emission tomography (PET) studies of mGluR5 using [

methodsFifteen amyloid positive participants with early AD and 12 amyloid negative, cognitively normal (CN) participants underwent PET scans with both [

resultsA strong positive correlation between mGluR5 and synaptic density was present in the hippocampus for participants with AD (r = 0.81, p < 0.001) and in the CN group (r = 0.74, p = 0.005). In the entorhinal cortex, there was a strong positive correlation between mGluR5 and synaptic density in the AD group (r = 0.85, p < 0.001), but a weaker non-significant correlation in the CN group (r = 0.36, p = 0.245). Exploratory analyses indicated more widespread significant positive correlations between synaptic density and mGluR5 within regions, as well as significant positive correlations between synaptic density in the temporal lobe and mGluR5 across a broader set of regions commonly affected by AD.

conclusionsOur findings suggest that mGluR5 reduction in AD is closely linked to synaptic loss. Longitudinal studies are needed to clarify causality, deepen understanding of AD pathogenesis, and aid in developing novel biomarkers and treatments.

Indexed as

Alzheimer DiseaseBrainPositron-Emission TomographyReceptor, Metabotropic Glutamate 5Receptors, Metabotropic GlutamateSynapsesAgedAged, 80 and overFemaleHumansMaleMembrane GlycoproteinsMiddle AgedRadiopharmaceuticalsGRM5 protein, humanMembrane GlycoproteinsRadiopharmaceuticalsReceptor, Metabotropic Glutamate 5Receptors, Metabotropic Glutamate[11C]UCB-J[18F]FPEBAlzheimer’s diseaseMGluR5 bindingPETSV2ASynaptic density

Identifiers

PMID40329311
PMCPMC12054321

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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.