ArticleNeuron2019
TREM2 Acts Downstream of CD33 in Modulating Microglial Pathology in Alzheimer's Disease.
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Article in Neuron, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 230 papers, 2 of them syntheses that pooled it.
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230citing papers in PubMed, 2 pooled it
21.7field-weighted citation impact, top 1% of its field
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Who cites it
230 citing papers in PubMed, 2 syntheses or guidelines pooled it, 384 citations in OpenAlex.
- Druggable genome-wide Mendelian randomization identifies therapeutic targets for metabolic dysfunction-associated steatotic liver disease.Lipids in health and disease · 2025Pooled it
- The Amyloid-β Pathway in Alzheimer's Disease.Molecular psychiatry · 2021Pooled it
- The TREM2 agonistic antibody AL002 in early Alzheimer's disease: a phase 2 randomized trial.Nature medicine · 2026Trial
- Preclinical and first-in-human evaluation of AL002, a novel TREM2 agonistic antibody for Alzheimer's disease.Alzheimer's research & therapy · 2024Trial
- Advances in Alzheimer's disease: mechanistic insights and therapeutic targets.Science China. Life sciences · 2026Review
- TREM2 plays a critical role in innate immune defense against acute Toxoplasma gondii infection by promoting macrophage antimicrobial activities.PLoS pathogens · 2026Article
- Repurposing trazodone for Alzheimer's disease to modulate soluble ST2 levels and alleviate Alzheimer's pathology.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- TREM2 in neurodegenerative diseases and acute neurological injuries: mechanisms to targeted therapies.Cell communication and signaling : CCS · 2026Review
- TREM2 in neurodegeneration and diseases.Molecular psychiatry · 2026Review
- Microglia and neuroinflammation: function, heterogeneity, and crosstalk.Cellular & molecular immunology · 2026Review
- Genome-wide pleiotropic analysis identifies shared genetic architecture within the cognition-immune nexus.Translational psychiatry · 2026Article
- Disruption of the brain-spleen axis impairs monocyte-microglia communication and accelerates disease progression in a mouse model of amyloidosis.Nature communications · 2026Article
- Review
- Shared transcriptomic signatures in perilesional and contralesional cortex after ischemic stroke.Journal of neuroinflammation · 2026Article
- Mechanisms of increased Alzheimer's disease pathology with R47H and R62H TREM2 variants.Acta neuropathologica · 2026Article
- Microglial ITAM & ITIM Signaling in Neurodegenerative Disease and Brain Aging.Journal of molecular biology · 2026Review
- Microglial CD31 suppresses Aβ clearance and promotes Alzheimer pathology in 5×FAD mice.Nature communications · 2026Article
- Article
- A diagnostic plasma omics-biomarker for Alzheimer's disease informed by microglial single-cell transcriptomics: A pilot study.bioRxiv : the preprint server for biology · 2026Article
- CD33 Isoform Splicing Dysregulation: A Molecular Determinant of Microglial Dysfunction in Alzheimer's Disease Pathology.Molecular neurobiology · 2026Review
170 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Ana GriciucGenetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Shaun PatelGenetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Anthony N FedericoGenetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Se Hoon ChoiGenetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Brendan J InnesGenetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Mary K OramGenetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Gea CereghettiGenetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA; Institute of Biochemistry, Department of Biology, ETH Zürich, 8093 Zürich, Switzerland.
Danielle McGintyGenetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Anthony AnselmoDepartment of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Ruslan I SadreyevDepartment of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Suzanne E HickmanCenter for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Joseph El KhouryCenter for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Marco ColonnaDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Rudolph E TanziGenetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA. Electronic address: tanzi@helix.mgh.harvard.edu.
Massachusetts General Hospital · USHarvard University · USWashington University in St. Louis · US
Funding
SEARCH FOR NOVEL ALZHEIMERS DISEASE GENESR01MH060009 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI TANZI, RUDOLPH EMILE · 1999 to 2017
$5.4MThe Neuroimmune System in Alzheimer's DiseaseRF1AG051506 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI EL-KHOURY, JOSEPH EL · 2015 to 2015
$3.8MCD33 and Alzheimer's Disease: from Biology to TherapyR00AG049056 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI GRICIUC, ANA · 2017 to 2019
$747kCD33 and Alzheimer's Disease: from Biology to TherapyK99AG049056 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI GRICIUC, ANA · 2015 to 2016
$274kNIA NIH HHS K99 AG049056NIA NIH HHS R00 AG049056NIA NIH HHS RF1 AG051506NIMH NIH HHS R01 MH060009
Abstract
The microglial receptors CD33 and TREM2 have been associated with risk for Alzheimer's disease (AD). Here, we investigated crosstalk between CD33 and TREM2. We showed that knockout of CD33 attenuated amyloid beta (Aβ) pathology and improved cognition in 5xFAD mice, both of which were abrogated by additional TREM2 knockout. Knocking out TREM2 in 5xFAD mice exacerbated Aβ pathology and neurodegeneration but reduced Iba1
Indexed as
CognitionAcute-Phase ReactionAlzheimer DiseaseAmyloid beta-PeptidesAnimalsBrainDisease Models, AnimalGene Expression RegulationInterleukin-6Interleukin-8Membrane GlycoproteinsMiceMice, KnockoutMicrogliaPhagocytosisPlaque, AmyloidAmyloid beta-PeptidesCd33 protein, mouseInterleukin-6interleukin-6, mouseInterleukin-8Membrane GlycoproteinsReceptors, ImmunologicSialic Acid Binding Ig-like Lectin 3Trem2 protein, mouseAlzheimer'samyloid betaCD33IL-1betamicroglianeuroinflammationpathway analysisRNA-seqtranscriptomicsTREM2
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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.