ArticleScience translational medicine2022
Reversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q.
2 registry-linked trialsOpen access · greenAbstract read
In one paragraph
Article in Science translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 60 papers.
0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
8.4field-weighted citation impact, top 2% of its field
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.
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.
A Phase 1B Multiple Ascending Dose Study of The Safety and Tolerability of BMS-984923 in Healthy Older Adults and Patients With Alzheimer's Disease
Synaptic Vesicle Glycoprotein 2A-PET/CT and PET/MRI Combined Clinical Criteria Score in the Diagnosis of Early Cognitive Alteration
Who cites it
60 citing papers in PubMed, 104 citations in OpenAlex.
- A pilot study to evaluate the effect of CT1812 treatment on synaptic density and other biomarkers in Alzheimer's disease.Alzheimer's research & therapy · 2024Trial
- Calcium dysregulation in neurovascular function in Alzheimer's disease: mechanisms, therapeutic targets.GeroScience · 2026Review
- Distinct Filament Conformation for Receptor-Bound Amyloid-β from Alzheimer's Disease Brain.Nature communications · 2026Article
- Repeated Intra-cisterna Magna Injections with Amyloid-beta Oligomers to Induce Alzheimer's Disease in Cynomolgus Monkey (Experimental neurobiology · 2026Article
- Insulin resistance alters cortical inhibitory neurons and microglia to exacerbate Alzheimer's knock-in mouse phenotypes.Molecular neurodegeneration · 2026Article
- Structural Assessment of Fibrillated Beta Amyloid to Reveal the Potential Epitopes for Alzheimer's Disease.Cell biochemistry and biophysics · 2026Article
- An engineered ROS-responsive cascade nanoplatform delays Alzheimer's disease progression via Nrf2/GPX4-mediated microglial functional reprogramming.Materials today. Bio · 2026Article
- Current progress in pathway-targeted therapeutics for Alzheimer's disease: mechanistic insights and windows of opportunity.Molecular and cellular biochemistry · 2026Review
- Presymptomatic pharmacological inhibition of mGluR5 improves survival in a mouse model of prion diseases.Acta neuropathologica communications · 2026Article
- Microglial pathological synaptic pruning in epilepsy: pathophysiology and therapeutic potential.Frontiers in immunology · 2026Review
- Microglia-Neuron Interactions in Alzheimer's Disease.Current neuropharmacology · 2026Review
- The complement cascade in Alzheimer's disease: modern implications of an ancient immune protagonist.Molecular neurodegeneration · 2025Review
- Comprehensive and Site-Specific Characterization of Protein N-Glycosylation in AD Samples Reveals Its Potential Roles in Protein Aggregation and Synaptic Dysfunction.Analytical chemistry · 2025Article
- Distinct Filament Conformation for Receptor-Bound Amyloid-ß from Alzheimer's Disease Brain.bioRxiv : the preprint server for biology · 2025Article
- Axon Regeneration and Functional Recovery after Spinal Cord Injury is Enhanced by Allele-Specific ApoE Neuronal Action through LRP8.bioRxiv : the preprint server for biology · 2025Article
- Targeting metabotropic glutamate receptors for symptomatic and disease-modifying treatment in Parkinson's disease.NPJ Parkinson's disease · 2025Review
- HSV-1 hijacks mitochondrial dynamics: potential molecular mechanisms linking viral infection to neurodegenerative disorders.Apoptosis : an international journal on programmed cell death · 2025Review
- Reduced synaptic vesicle protein 2A in extracellular vesicles and brains of Alzheimer's disease: associations with Aβ, tau, synaptic proteins and APOE ε4.Translational neurodegeneration · 2025Article
- Insulin resistance alters cortical inhibitory neurons and microglia to exacerbate Alzheimer's knock-in mouse phenotypes.bioRxiv : the preprint server for biology · 2025Article
- [Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025Article
Corrections and comments
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Authors and funding
22 authors at 2 institutions in 2 countries.
Joshua SpurrierCellular Neuroscience, Neurodegeneration and Repair Program, Departments of Neurology and Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA.ORCID 0000-0002-6267-7231
LaShae NicholsonCellular Neuroscience, Neurodegeneration and Repair Program, Departments of Neurology and Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA.ORCID 0000-0002-5171-181X
Xiaotian T FangYale PET Center, Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06510, USA.ORCID 0000-0001-9706-1122
Austin J StonerCellular Neuroscience, Neurodegeneration and Repair Program, Departments of Neurology and Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA.ORCID 0000-0002-3788-9347
Takuya ToyonagaYale PET Center, Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06510, USA.ORCID 0000-0002-0369-8294
Daniel HoldenYale PET Center, Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06510, USA.
Timothy R SiegertAllyx Therapeutics Inc., New Haven, CT 06513, USA.ORCID 0000-0002-3055-443X
William LairdCellular Neuroscience, Neurodegeneration and Repair Program, Departments of Neurology and Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA.
Mary Alice AllnuttCellular Neuroscience, Neurodegeneration and Repair Program, Departments of Neurology and Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA.
Marius ChiasseuCellular Neuroscience, Neurodegeneration and Repair Program, Departments of Neurology and Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA.
A Harrison BrodyCellular Neuroscience, Neurodegeneration and Repair Program, Departments of Neurology and Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA.ORCID 0000-0001-9655-6713
Hideyuki TakahashiCellular Neuroscience, Neurodegeneration and Repair Program, Departments of Neurology and Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA.
Sarah Helena NiesCellular Neuroscience, Neurodegeneration and Repair Program, Departments of Neurology and Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA.ORCID 0000-0002-5619-1454
Azucena Pérez-CañamásCellular Neuroscience, Neurodegeneration and Repair Program, Departments of Neurology and Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA.ORCID 0000-0003-3635-6298
Pragalath SadasivamYale PET Center, Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06510, USA.
Supum LeeYale PET Center, Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06510, USA.ORCID 0000-0002-5017-9032
Songye LiYale PET Center, Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06510, USA.ORCID 0000-0002-6096-8756
Le ZhangCellular Neuroscience, Neurodegeneration and Repair Program, Departments of Neurology and Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA.ORCID 0000-0002-4860-831X
Yiyun H HuangYale PET Center, Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06510, USA.
Richard E CarsonYale PET Center, Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06510, USA.ORCID 0000-0002-9338-7966
Zhengxin CaiYale PET Center, Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06510, USA.ORCID 0000-0002-2005-6760
Stephen M StrittmatterCellular Neuroscience, Neurodegeneration and Repair Program, Departments of Neurology and Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA.ORCID 0000-0001-8188-3092
Yale University · USAlly Therapeutics (United States) · US
Funding
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MYale Alzheimer Disease Research CenterP30AG066508 · NIA · YALE UNIVERSITY · PI Jaime Grutzendler · 2020 to 2026
$30.2MInterdepartmental Neuroscience Program (INP)T32NS041228 · NINDS · YALE UNIVERSITY · PI Charles A Greer, Marina R Picciotto · 2001 to 2026
$12.0MPrion Protein in Alzheimer's Disease PathophysiologyR01AG034924 · NIA · YALE UNIVERSITY · PI STEPHEN M STRITTMATTER · 2010 to 2026
$9.6MSilent Allosteric Modulation of mGluR5 for Safe and Effective Therapy of Alzheimer's DiseaseU01AG058608 · NIA · YALE UNIVERSITY · PI STRITTMATTER, STEPHEN M · 2018 to 2022
$8.5MNEUROBIOLOGY OF CORTICAL SYSTEMST32NS007224 · NINDS · YALE UNIVERSITY · PI CARDIN, JESSICA A · 1985 to 2025
$4.6MOverlapping Molecular Dysregulation of Endolysosomal Function in Alzheimer's Disease and FTLD-TDPR01AG066165 · NIA · YALE UNIVERSITY · PI STRITTMATTER, STEPHEN M · 2019 to 2023
$3.9MSex-Specific Single Cell Expression Profiles, Genetic Risk and Drug Responsiveness in Alzheimer's DiseaseR56AG074015 · NIA · YALE UNIVERSITY · PI GHOSH, SOURAV, ROTHLIN, CARLA · 2021 to 2022
$2.5MDevelopment of PET imaging probes for ROCK2R01AG069921 · NIA · YALE UNIVERSITY · PI CAI, ZHENGXIN · 2021 to 2023
$2.5MSynaptic selectivity for microglial-mediated damage in Alzheimer's DiseaseRF1AG070926 · NIA · YALE UNIVERSITY · PI STRITTMATTER, STEPHEN M · 2021 to 2021
$2.4MElucidating the role of AD risk factor Pyk2 in tau-induced synaptic dysfunctionF31AG066483 · NIA · YALE UNIVERSITY · PI BRODY, ALEX HARRISON · 2020 to 2021
$81kNCATS NIH HHS UL1 TR001863NIA NIH HHS F31 AG066483NIA NIH HHS P30 AG066508NIA NIH HHS R01 AG034924NIA NIH HHS R01 AG066165NIA NIH HHS R01 AG069921NIA NIH HHS R56 AG074015NIA NIH HHS RF1 AG070926NIA NIH HHS U01 AG058608NINDS NIH HHS T32 NS007224NINDS NIH HHS T32 NS041228
Abstract
Microglia-mediated synaptic loss contributes to the development of cognitive impairments in Alzheimer's disease (AD). However, the basis for this immune-mediated attack on synapses remains to be elucidated. Treatment with the metabotropic glutamate receptor 5 (mGluR5) silent allosteric modulator (SAM), BMS-984923, prevents β-amyloid oligomer-induced aberrant synaptic signaling while preserving physiological glutamate response. Here, we show that oral BMS-984923 effectively occupies brain mGluR5 sites visualized by [
Indexed as
Alzheimer DiseaseReceptor, Metabotropic Glutamate 5AnimalsComplement C1qDisease Models, AnimalMiceSynapsesComplement C1qReceptor, Metabotropic Glutamate 5
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
NCT05804383ClinicalTrials.gov
NCT06445582ClinicalTrials.gov
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.