Evidence map›Paper›PMID 40491249›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Cerebrospinal fluid and brain positron emission tomography measures of synaptic vesicle glycoprotein 2A: Biomarkers of synaptic density in Alzheimer's disease.

Adam P Mecca, Nicholas J Ashton, Ming-Kai Chen, Ryan S O'Dell, Takaya Toyonaga, Wenzhen Zhao, Juan J Young, Elaheh Salardini, Kara A Bates, Jocelyn Ra and 14 more

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In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–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

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
  4. Article
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

24 authors.

Adam P MeccaAlzheimer's Disease Research Unit, Yale School of Medicine, New Haven, Connecticut, USA.
Nicholas J AshtonDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Ming-Kai ChenDepartment of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut, USA.
Ryan S O'DellAlzheimer's Disease Research Unit, Yale School of Medicine, New Haven, Connecticut, USA.
Takaya ToyonagaDepartment of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut, USA.
Wenzhen ZhaoAlzheimer's Disease Research Unit, Yale School of Medicine, New Haven, Connecticut, USA.
Juan J YoungAlzheimer's Disease Research Unit, Yale School of Medicine, New Haven, Connecticut, USA.
Elaheh SalardiniAlzheimer's Disease Research Unit, Yale School of Medicine, New Haven, Connecticut, USA.
Kara A BatesAlzheimer's Disease Research Unit, Yale School of Medicine, New Haven, Connecticut, USA.
Jocelyn RaAlzheimer's Disease Research Unit, Yale School of Medicine, New Haven, Connecticut, USA.
Sam GoodcaseAlzheimer's Disease Research Unit, Yale School of Medicine, New Haven, Connecticut, USA.
Jason A Silva-RudbergAlzheimer's Disease Research Unit, Yale School of Medicine, New Haven, Connecticut, USA.
Nabeel B NabulsiDepartment of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut, USA.
Ann BrinkmalmDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Hlin KvartsbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Michael SchöllDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Johanna NilssonDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Amy F T ArnstenAlzheimer's Disease Research Unit, Yale School of Medicine, New Haven, Connecticut, USA.
Yiyun HuangDepartment of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut, USA.
Oskar HanssonClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Richard E CarsonDepartment of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut, USA.
Kaj BlennowDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Christopher H van DyckAlzheimer's Disease Research Unit, Yale School of Medicine, New Haven, Connecticut, USA.

Funding

Yale Study Support Suite (YES3): Dashboard and Web Portal Software Supporting Research Workflow through integrated, customizable REDCap External ModulesP30AG021342 · NIA · YALE UNIVERSITY · PI Albert C Shaw · 2002 to 2026
$37.9M
Yale University Clinical and Translational Science Award ProgramUL1TR000142 · NCATS · YALE UNIVERSITY · PI SHERWIN, ROBERT S · 2012 to 2015
$31.8M
Yale Alzheimer Disease Research CenterP30AG066508 · NIA · YALE UNIVERSITY · PI STEPHEN M STRITTMATTER, CHRISTOPHER H VAN DYCK · 2020 to 2026
$30.2M
Yale Alzheimer Disease Research CenterP50AG047270 · NIA · YALE UNIVERSITY · PI MAROTTOLI, RICHARD · 2015 to 2019
$8.3M
Clinical Neuroscience Research Training Program in PsychiatryT32MH019961 · NIMH · YALE UNIVERSITY · PI Christopher John Pittenger · 1996 to 2026
$5.9M
PET Imaging of SV2A and Other Biomarkers in Alzheimer's DiseaseR01AG062276 · NIA · YALE UNIVERSITY · PI VAN DYCK, CHRISTOPHER H · 2018 to 2022
$5.5M
A Pilot Synaptic Vesicle Glycoprotein 2A (SV2A) PET Study to Evaluate the Effect of CT1812 Treatment on Synaptic Density in Subjects with Mild to Moderate Alzheimer's DiseaseRF1AG057553 · NIA · COGNITION THERAPEUTICS, INC. · PI CATALANO, SUSAN M · 2017 to 2020
$4.8M
Neighborhood Socioeconomic Contextual Disadvantage and Alzheimer's DiseaseRF1AG057784 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI BENDLIN, BARBARA BRIGITTA, KIND, AMY J. · 2017 to 2017
$3.8M
PET Imaging of Synaptic Density in Alzheimers DiseaseR01AG052560 · NIA · YALE UNIVERSITY · PI CARSON, RICHARD E., VAN DYCK, CHRISTOPHER H · 2017 to 2020
$3.2M
AD Strategic Fund and the Alzheimer's Association #ADSF-21-831376-CAD Strategic Fund and the Alzheimer's Association #ADSF-21-831377-CAD Strategic Fund and the Alzheimer's Association #ADSF-21-831381-CAD Strategic Fund and the Alzheimer's Association #ADSF-24-1284328-CALF-agreement #ALFGBG-715986ALF-agreement #ALFGBG-965240Alzheimer's Association SG-23-1038904 QCAlzheimer's Association 2021 Zenith ZEN-21-848495Alzheimer's Drug Discovery Foundation #201809-2016862anonymous donorat UCL UKDRI-1003Bluefield ProjectClinical Neuroscience Research Training in PsychiatryCTSA UL1TR000142Cure Alzheimer's FundErling-Persson Family FoundationEuropean Partnership on MetrologyEuropean Union Joint Program for Neurodegenerative Disorders JPND2019-466-236European Union Joint Programme - Neurodegenerative Disease Research JPND2021-00694European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement 860197European Union's Horizon Europe Research and Innovation ProgrammeFamiljen Rönströms StiftelseHjärnfonden #FO2017-0243Kirsten and Freddy Johansen FoundationLa Fondation Recherche AlzheimerNational Center for Advancing Translational ScienceNational Institute for Health and Care Research University College London Hospitals Biomedical Research CentreNCATS NIH HHS UL1 TR000142NEuroBioStand #22HLT07NIA NIH HHS K23AG057784NIA NIH HHS P30 AG021342NIA NIH HHS P30AG021342NIA NIH HHS P30 AG066508NIA NIH HHS P30AG066508NIA NIH HHS P50 AG047270NIA NIH HHS P50AG047270NIA NIH HHS R01 AG052560NIA NIH HHS R01AG052560NIA NIH HHS R01 AG062276NIA NIH HHS R01AG062276NIA NIH HHS RF1 AG057553NIA NIH HHS RF1AG057553NIA NIH HHS RF1 AG057784NIMH NIH HHS T32 MH019961Olav Thon FoundationParticipating StatesRuth L. Kirschstein National Research Service AwardStiftelsen för Gamla TjänarinnorSwedish Alzheimer Foundation #AF-930351Swedish Alzheimer Foundation #AF-939721Swedish Alzheimer Foundation #AF-968270Swedish Alzheimer Foundation #AF-994551Swedish Research Council #2017-00915Swedish Research Council #2019-02397Swedish Research Council #2022-01018Swedish State Support for Clinical Research #ALFGBG-71320Swedish state under the agreement between the Swedish government and the County CouncilsUK Dementia Research Institute
6 · The paper itself

Abstract

introductionPositron emission tomography (PET) imaging with ligands for synaptic vesicle glycoprotein 2A (SV2A) has emerged as a promising methodology for measuring synaptic density in Alzheimer's disease (AD). We investigated associations between SV2A concentrations in the brain and cerebrospinal fluid (CSF).

methodsTwenty-one participants with early AD and 7 cognitively normal (CN) individuals underwent [

resultsCSF SV2A was lower in AD compared to CN participants. Within the AD group, CSF SV2A was highly correlated with SV2A PET. By contrast, other CSF proteins were generally higher in participants with AD and not associated with SV2A PET. DISCUSSION: We report a novel CSF assay for SV2A that is strongly correlated with the PET measurement of SV2A. Our results suggest that CSF SV2A may serve as a biomarker for synaptic density in AD. HIGHLIGHTS: Synaptic vesicle glycoprotein 2A (SV2A) measured by a novel cerebrospinal fluid (CSF) enzyme-linked immunosorbent assay (ELISA) was lower in participants with symptomatic Alzheimer's disease (AD). CSF SV2A was highly correlated with SV2A measured by positron emission tomography (PET) in participants with AD. Other CSF synaptic/axonal proteins were not significantly associated with SV2A PET. CSF SV2A may serve as a biomarker for synaptic density in AD.

Indexed as

Alzheimer DiseaseBrainMembrane GlycoproteinsNerve Tissue ProteinsPositron-Emission TomographySynapsesAgedAged, 80 and overBiomarkersEnzyme-Linked Immunosorbent AssayFemaleHumansMaleMiddle AgedBiomarkersMembrane GlycoproteinsNerve Tissue ProteinsSV2A protein, humanAlzheimer's diseasebiomarkersCSFSV2Asynaptic density

Identifiers

PMID40491249
PMCPMC12149441

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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.