ArticleThe Journal of experimental medicine2020
Anti-human TREM2 induces microglia proliferation and reduces pathology in an Alzheimer's disease model.
Article in The Journal of experimental medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 316 papers, 3 of them syntheses that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
316 citing papers in PubMed, 3 syntheses or guidelines pooled it, 538 citations in OpenAlex.
- Gain-of-function Modulation of TREM2 and its Impact on Amyloid-β and Tau Pathologies in Alzheimer's Disease: A Systematic Review and Meta-analysis of Animal Studies.Molecular neurobiology · 2026Pooled it
- Unraveling the Controversy: The Causal Link Between Osteoarthritis and Alzheimer's Disease.Brain and behavior · 2025Pooled it
- Osteopontin in Alzheimer's Disease: A Double-Edged Sword in Neurodegeneration and Neuroprotection-A Systematic Review.CNS neuroscience & therapeutics · 2025Pooled it
- Phase 1, First-In-Human, Single-/Multiple-Ascending Dose Study of Iluzanebart in Healthy Volunteers.Annals of clinical and translational neurology · 2025Trial
- Preclinical and first-in-human evaluation of AL002, a novel TREM2 agonistic antibody for Alzheimer's disease.Alzheimer's research & therapy · 2024Trial
- Article
- CD11c + microglia: From basic research to clinical application.Neural regeneration research · 2026Article
- Graphene Quantum Dots in Neurodegeneration: Protein Aggregation and the Microglial State as Therapeutic Targets.Nanomaterials (Basel, Switzerland) · 2026Review
- Batch- and Composition-Controlled Reanalysis of Bulk and Single-Nucleus Transcriptomes Reveals Co-Enrichment of Glial Complement and of Translational Signatures in Parkinson's Disease and Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2026Article
- M2-associated microglial states in oligodendrocyte regulation and white matter repair in vascular dementia.Journal of translational medicine · 2026Review
- Alzheimer's Disease in the Era of Geroscience: Mechanisms, Biomarkers, and Therapeutic Prospects.Cells · 2026Review
- TMEM59 regulates microglial Aβ phagocytosis in a TREM2-dependent manner and acts as a potential therapeutic target for Aβ amyloidosis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Context-dependent roles of osteopontin in aging-related neurological disorders.The Journal of international medical research · 2026Review
- TREM2-mediated Crosstalk in ALS: Microglial Fate Transition, Protein Aggregate Clearance, and Peripheral Nerve Repair.Neuroscience bulletin · 2026Article
- Targeting Mitochondrial Dysfunction in Microglia: A New Frontier for Treating Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Neuroinflammation in Alzheimer's and Parkinson's diseases: pathogenic mechanisms and therapeutic strategies.Translational neurodegeneration · 2026Review
- Review
- TREM2 in neurodegenerative diseases and acute neurological injuries: mechanisms to targeted therapies.Cell communication and signaling : CCS · 2026Review
- Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies.Cell · 2026Review
- Review
256 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
TREM2 is a receptor for lipids expressed in microglia. The R47H variant of human TREM2 impairs ligand binding and increases Alzheimer's disease (AD) risk. In mouse models of amyloid β (Aβ) accumulation, defective TREM2 function affects microglial response to Aβ plaques, exacerbating tissue damage, whereas TREM2 overexpression attenuates pathology. Thus, AD may benefit from TREM2 activation. Here, we examined the impact of an anti-human TREM2 agonistic mAb, AL002c, in a mouse AD model expressing either the common variant (CV) or the R47H variant of TREM2. Single-cell RNA-seq of microglia after acute systemic administration of AL002c showed induction of proliferation in both CV- and R47H-transgenic mice. Prolonged administration of AL002c reduced filamentous plaques and neurite dystrophy, impacted behavior, and tempered microglial inflammatory response. We further showed that a variant of AL002c is safe and well tolerated in a first-in-human phase I clinical trial and engages TREM2 based on cerebrospinal fluid biomarkers. We conclude that AL002 is a promising candidate for AD therapy.
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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.