ArticleSignal transduction and targeted therapy2023
Fc effector of anti-Aβ antibody induces synapse loss and cognitive deficits in Alzheimer's disease-like mouse model.
Article in Signal transduction and targeted therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Passive amyloid-β immunotherapy in Alzheimer's disease: a multicellular clearance system beyond plaque removal.Molecular neurodegeneration · 2026Review
- Could the cognitive benefits of amyloid-beta clearance grow in time for Alzheimer's disease?Translational psychiatry · 2026Review
- An anti-inflammatory neuroenhancer mitigates amyloid-β pathology to improve Alzheimer's disease therapy.Materials today. Bio · 2026Article
- Amyloid-related imaging abnormalities (ARIA) in anti-amyloid therapies for Alzheimer's disease: An update from the Alzheimer's Association ARIA workgroup.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Microglia-Neuron Interactions in Alzheimer's Disease.Current neuropharmacology · 2026Review
- Anti-inflammatory CAR-microglia targeting Aβ for Alzheimer's disease therapy.Frontiers in immunology · 2026Article
- The Alzheimer's therapeutic Lecanemab attenuates Aβ pathology by inducing an amyloid-clearing program in microglia.Nature neuroscience · 2026Article
- Article
- Attenuating α-synuclein pathology in mice with in situ engineered astrocytes.Translational neurodegeneration · 2025Article
- N-acetylcysteine (NAC) ameliorates ethanol-induced oxidative stress, neuroinflammation, and cognitive dysfunction in APP/PS1 mouse model.Translational psychiatry · 2025Article
- MS4A6A/Ms4a6d deficiency disrupts neuroprotective microglia functions and promotes inflammation in Alzheimer's disease model.Molecular neurodegeneration · 2025Article
- Tau, synapse loss and gliosis progress in an Alzheimer's mouse model after amyloid-β immunotherapy.Brain : a journal of neurology · 2025Article
- CD22 modulation alleviates amyloid β-induced neuroinflammation.Journal of neuroinflammation · 2025Article
- Neuroinflammation in Alzheimer's disease: insights from peripheral immune cells.Immunity & ageing : I & A · 2024Review
- Recombinant Antibody Fragments for Immunotherapy of Parkinson's Disease.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- Recombinant Antibody Fragments for Neurological Disorders: An Update.Current neuropharmacology · 2024Review
- DaiTongXiao improves gout nephropathy by inhibiting inflammatory response through the TLR4/MyD88/NF-κB pathway.Frontiers in pharmacology · 2024Article
- Microglia in pediatric brain tumors: The missing link to successful immunotherapy.Cell reports. Medicine · 2023Review
- Amyloid β-based therapy for Alzheimer's disease: challenges, successes and future.Signal transduction and targeted therapy · 2023Review
- Baseline plasma C1q and C3 as potential biomarkers for lecanemab efficacy and ARIA risk in early Alzheimer's disease.Alzheimer's & dementia (New York, N. Y.)Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Passive immunotherapy is one of the most promising interventions for Alzheimer's disease (AD). However, almost all immune-modulating strategies fail in clinical trials with unclear causes although they attenuate neuropathology and cognitive deficits in AD animal models. Here, we showed that Aβ-targeting antibodies including their lgG1 and lgG4 subtypes induced microglial engulfment of neuronal synapses by activating CR3 or FcγRIIb via the complex of Aβ, antibody, and complement. Notably, anti-Aβ antibodies without Fc fragment, or with blockage of CR3 or FcγRIIb, did not exert these adverse effects. Consistently, Aβ-targeting antibodies, but not their Fab fragments, significantly induced acute microglial synapse removal and rapidly exacerbated cognitive deficits and neuroinflammation in APP/PS1 mice post-treatment, whereas the memory impairments in mice were gradually rescued thereafter. Since the recovery rate of synapses in humans is much lower than that in mice, our findings may clarify the variances in the preclinical and clinical studies assessing AD immunotherapies. Therefore, Aβ-targeting antibodies lack of Fc fragment, or with reduced Fc effector function, may not induce microglial synaptic pruning, providing a safer and more efficient therapeutic alternative for passive immunotherapy for AD.
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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.