Evidence map›Paper›PMID 25792098›Full record

ReviewThe Lancet. Neurology2015

Neuroinflammation in Alzheimer's disease.

Michael T Heneka, Monica J Carson, Joseph El Khoury, Gary E Landreth, Frederic Brosseron, Douglas L Feinstein, Andreas H Jacobs, Tony Wyss-Coray, Javier Vitorica, Richard M Ransohoff and 27 more

3 registry-linked trialsOpen access · greenAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in The Lancet. Neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 3,461 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3,461citing papers in PubMed, 3 pooled it
206.4field-weighted citation impact, top 1% 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.

NCT04381468 phase1 / phase2completednot on this mapstarted 2021, after this paper: background citation

SEMA4D Blockade Safety and Brain Metabolic Activity in Alzheimer's Disease (AD): A Multi-center, Randomized, Double-Blind, Placebo-Controlled Safety and Biomarker Study of Pepinemab Anti-SEMA4D Antibody in Early-AD

TypeinterventionalSponsorVaccinex Inc.Ran2021 to 2024Enrolled50ConditionsAlzheimer DiseaseArmsPepinemab, Placebo
NCT05050812 naunknown statusnot on this mapstarted 2021, after this paper: background citation

The Grounded Brain: How Sleeping Grounded (Earthing) Affects Cognition and Personal Perceptions in Participants With Mild Cognitive Impairment Due to Alzheimer's Disease (MCI/AD)

TypeinterventionalSponsorCalifornia Institute of Integral StudiesRan2021 to 2021Enrolled8ConditionsMild Cognitive Impairment, Chronic InflammationArmsgrounding mat
NCT06639282 phase2recruitingnot on this mapstarted 2025, after this paper: background citation

SIPO1-AD: A Phase II Clinical Trial for the Assessment of Safety, Tolerability, and Efficacy of Siponimod in Patients With Mild Alzheimer's Disease

TypeinterventionalSponsorSt. Joseph's Hospital and Medical Center, PhoenixRan2025 to 2029Enrolled105ConditionsAlzheimer Disease, Mild Alzheimer Disease, MCI With Increased Risk for Alzheimer Disease, Cognitive Impairment, MildArmsSiponimod, Placebo
3 · Its place in the literature

Who cites it

3,461 citing papers in PubMed, 3 syntheses or guidelines pooled it, 5,891 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. Review

3,401 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

37 authors at 20 institutions in 12 countries.

Michael T HenekaDepartment of Neurology, University Hospital Bonn, University of Bonn, Bonn, Germany; German Center for Neurodegnerative Diseases (DZNE), Bonn, Germany. Electronic address: michael.heneka@ukb.uni-bonn.de.
Monica J CarsonDivision of Biomedical Sciences, Center for Glial-Neuronal Interactions, University of California, Riverside, CA, USA.
Joseph El KhouryDivision of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Gary E LandrethAlzheimer Research Laboratory, Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Frederic BrosseronGerman Center for Neurodegnerative Diseases (DZNE), Bonn, Germany.
Douglas L FeinsteinDepartment of Anesthesiology, University of Illinois, Chicago, IL, USA.
Andreas H JacobsDepartment of Geriatrics, Johanniter Hospital, Bonn, Germany; European Institute for Molecular Imaging (EIMI) at the Westfalian Wilhelms University (WWU), Münster, Germany.
Tony Wyss-CorayDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA; Center for Tissue Regeneration, Repair, and Restoration, VA Palo Alto Health Care System, Palo Alto, CA, USA.
Javier VitoricaInstituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocio, Consejo Superior de Investigaciones Cientificas Universidad de Sevilla, Sevilla, Spain.
Richard M RansohoffDepartment of Neuroscience, Neuroinflammation Research Center, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Karl HerrupDivision of Life Science, Hong Kong University of Science and Technology, Hong Kong.
Sally A FrautschyDepartment of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, the Geriatric, Research, and Clinical Center, Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, CA, USA.
Bente FinsenInstitute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Guy C BrownDepartment of Biochemistry, University of Cambridge, Cambridge, UK.
Alexei VerkhratskyFaculty of Life Sciences, The University of Manchester, Manchester, UK; Achucarro Center for Neuroscience, Basque Foundation for Science (IKERBASQUE), Bilbao, Spain; Department of Neurosciences, University of the Basque Country UPV/EHU (Euskal Herriko Unibertsitatea/Universidad del País Vasco) and CIBERNED (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas), Leioa, Spain.
Koji YamanakaResearch Institute of Environmental Medicine, Nagoya University/RIKEN Brain Science Institute, Wako-shi, Japan.
Jari KoistinahoDepartment of Neurobiology, AI Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Eicke LatzGerman Center for Neurodegnerative Diseases (DZNE), Bonn, Germany; Institute of Innate Immunity, University of Bonn, Bonn, Germany; Department of InfectiousDiseases and Immunology, University of Massachusetts Medical School, Worcester, MA, USA.
Annett HalleMax-Planck Research Group Neuroimmunology, Center of Advanced European Studies and Research (CAESAR), Bonn, Germany.
Gabor C PetzoldDepartment of Neurology, University Hospital Bonn, University of Bonn, Bonn, Germany; German Center for Neurodegnerative Diseases (DZNE), Bonn, Germany.
Terrence TownZilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Dave MorganDepartment of Molecular Pharmacology and Physiology, Byrd Alzheimer's Institute, University of South Florida College of Medicine, Tampa, FL, USA.
Mari L ShinoharaDepartment of Immunology, Duke University Medical Center, Durham, NC, USA.
V Hugh PerrySchool of Biological Sciences, Southampton General Hospital, Southampton, UK.
Clive HolmesClinical and Experimental Science, University of Southampton, Southampton, UK; Memory Assessment and Research Centre, Moorgreen Hospital, Southern Health Foundation Trust, Southampton, UK.
Nicolas G BazanLouisiana State University Neuroscience Center of Excellence, Louisiana State University Health Sciences Center School of Medicine in New Orleans, LA, USA.
David J BrooksDivision of Experimental Medicine, Imperial College London, Hammersmith Hospital, London, UK.
Stéphane HunotCentre National de la Recherche Scientifique (CNRS), UMR 7225, Experimental Therapeutics of Neurodegeneration, Paris, France.
Bertrand JosephDepartment of Oncology Pathology, Cancer Centrum Karolinska, Karolinska Institutet, Stockholm, Sweden.
Nikolaus DeigendeschDepartment of Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin, Germany.
Olga GaraschukInstitute of Physiology II, Eberhard Karls University of Tübingen, Tübingen, Germany.
Erik BoddekeDepartment of Neuroscience, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands.
Charles A DinarelloDepartment of Medicine, University of Colorado Denver, Aurora, CO, USA.
John C BreitnerCentre for Studies on Prevention of Alzheimer's Disease, Douglas Mental Health University Institute, and the McGill University Faculty of Medicine, Montreal, Quebec, Canada.
Greg M ColeDepartment of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, the Geriatric, Research, and Clinical Center, Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, CA, USA.
Douglas T GolenbockDepartment of InfectiousDiseases and Immunology, University of Massachusetts Medical School, Worcester, MA, USA.
Markus P KummerDepartment of Neurology, University Hospital Bonn, University of Bonn, Bonn, Germany.
University of Bonn · DEUniversity of California, Los Angeles · USCenter of Advanced European Studies and Research · DECentre National de la Recherche Scientifique · FRCleveland Clinic Lerner College of Medicine · USConsejo Superior de Investigaciones Científicas · ESDouglas Mental Health University Institute · CADuke Medical Center · USGerman Center for Neurodegenerative Diseases · DEHammersmith Hospital · GBHarvard University · USHong Kong University of Science and Technology · HKIkerbasque · ESKarolinska Institutet · SELouisiana State University Health Sciences Center New Orleans · USMax Planck Institute for Infection Biology · DEMoorgreen Hospital · GBRIKEN Center for Brain Science · JPSouthampton General Hospital · GBUniversity Medical Center Groningen · NL

Funding

Peripheral TGF-beta Pathway Inhibitor Therapy in Alzheimer's RatsR01NS076794 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CHANG, KAREN T, CHEN, JEANNIE · 2011 to 2021
$4.9M
Preclinical Pharmacogenomics and Synaptic Biomarkers for Alzheimer's DiseaseR01AT006816 · NCCIH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI COLE, GREGORY M, FRAUTSCHY, SALLY ANN · 2011 to 2015
$1.9M
CD36 in Alzheimer's DiseaseR01NS059005 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI EL-KHOURY, JOSEPH EL · 2008 to 2012
$1.8M
Human tau neurodegeneration in Alzheimer'sR01AG021975 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FRAUTSCHY, SALLY ANN · 2004 to 2008
$1.2M
Diet and Exercise (DE) Program for Alzheimer PreventionRC1AG035878 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI COLE, GREGORY M, FRAUTSCHY, SALLY ANN · 2009 to 2010
$1.0M
Rebalancing Innate Immunity in Alzheimer's disease by deleting IRAK-MR21AG053884 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI TOWN, TERRENCE C · 2016 to 2017
$454k
Polyphenolic Interventions for tau Pathogenesis in Alzheimers ModelsI01BX001257 · VA · VA GREATER LOS ANGELES HEALTHCARE SYSTEM · PI FRAUTSCHY, SALLY ANN · 2013 to 2016
–
Medical Research Council MR/L010593/1NIA NIH HHS R21 AG053884NINDS NIH HHS R01 NS059005NINDS NIH HHS R01 NS076794
6 · The paper itself

Abstract

Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease.

Indexed as

Alzheimer DiseaseImmunity, InnateAnimalsAnti-Inflammatory Agents, Non-SteroidalAstrocytesBiomarkersBrain InjuriesClinical Trials as TopicDisease Models, AnimalDisease ProgressionHumansImmunizationInflammationInflammation MediatorsLocus CoeruleusMicrogliaAnti-Inflammatory Agents, Non-SteroidalBiomarkersInflammation MediatorsNootropic Agents

Identifiers

PMID25792098
PMCPMC5909703
OpenAlexW2087243986

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.