ArticleNature neuroscience2026
The Alzheimer's therapeutic Lecanemab attenuates Aβ pathology by inducing an amyloid-clearing program in microglia.
Article in Nature neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis 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.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Quantitative Systems Pharmacology Models of Anti-Amyloid Treatments for Alzheimer's Disease: A Systematic Review.CPT: pharmacometrics & systems pharmacology · 2026Pooled it
- Article
- A reproducible three-dimensional model of human brain tissue to investigate physiological and disease-associated microglia phenotypes.Nature neuroscience · 2026Article
- Passive immunotherapy for Parkinson's disease in 2025: Status and perspective.Neural regeneration research · 2026Article
- Review
- Passive amyloid-β immunotherapy in Alzheimer's disease: a multicellular clearance system beyond plaque removal.Molecular neurodegeneration · 2026Review
- Breaking the glial loop: astrocytic PAD2 and citrullinated vimentin drive microglial dysfunction in Alzheimer's disease.Molecular neurodegeneration · 2026Article
- Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies.Cell · 2026Review
- Treatment with KCL-286, a first-in-class retinoic acid receptor-β (RARβ) agonist, ameliorates neuronal DNA damage and inflammation in a mouse model of Alzheimer's disease.FEBS open bio · 2026Article
- Osteopontin in the Central Nervous System: Roles in Development, Injury, Neurodegeneration, and Neuro-Oncology.Biomolecules · 2026Review
- Microglial checkpoint collapse in Alzheimer's disease: a tri-axial framework for biomarker-informed neuroimmune therapy.Journal of neuroinflammation · 2026Review
- Lecanemab treatment improves B cell subpopulation immune homeostasis in patients with Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Anti-amyloid immunotherapy drives APOE4 specific increases in glial reactivity, perivascular immune activation, and ARIA-like events.bioRxiv : the preprint server for biology · 2026Article
- Article
- Neuropathological study of the effects of aducanumab anti-Aβ immunotherapy on patients with Alzheimer's disease.Acta neuropathologica · 2026Article
- Impact of Sema3A Interference on Cerebellum-Dependent Motor Associative Learning and Memory.International journal of molecular sciences · 2026Article
- Human microglial transitions at the Aβ-tau inflection point associate with divergent pathways to dementia and resilience.Nature medicine · 2026Article
- Age-related behavioral and molecular landmarks in new mouse models for studying Alzheimer's disease in Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- A model-based prion vaccine protects a transgenic mouse line carrying a Gerstmann-Sträussler-Scheinker disease mutation.Acta neuropathologica · 2026Article
- Research progress on Alzheimer's disease vaccines: from Aβ-targeted approaches to clinical translation.Frontiers in aging · 2026Review
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
Controversies over anti-amyloid immunotherapies underscore the need to elucidate their mechanisms of action. Here we demonstrate that Lecanemab, a leading anti-β-amyloid (Aβ) antibody, mediates amyloid clearance by activating microglial effector functions. Using a human microglia xenograft mouse model, we show that Lecanemab significantly reduces Aβ pathology and associated neuritic damage, while neither fragment crystallizable (Fc)-silenced Lecanemab nor microglia deficiency elicits this effect despite intact plaque binding. Single-cell RNA sequencing and spatial transcriptomic analyses reveal that Lecanemab induces a focused transcriptional program that enhances phagocytosis, lysosomal degradation, metabolic reprogramming, interferon γ genes and antigen presentation. Finally, we identify SPP1/osteopontin as a major factor induced by Lecanemab treatment and demonstrate its role in promoting Aβ clearance. These findings highlight that effective amyloid removal depends on the engagement of microglia through the Fc fragment, providing critical insights for optimizing anti-amyloid therapies in Alzheimer's disease.
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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.