ArticlePloS one2011
Chronic intranasal treatment with an anti-Aβ(30-42) scFv antibody ameliorates amyloid pathology in a transgenic mouse model of Alzheimer's disease.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed.
- Redefining intranasal brain delivery: from nasal entry to meaningful parenchymal and cellular exposure.Drug delivery · 2026Review
- Effective Nose-to-Brain Delivery of Blood-Brain Barrier Impermeant Anti-IL-1β Antibody via the Minimally Invasive Nasal Depot (MIND) Technique.ACS applied materials & interfaces · 2024Article
- Lead Acetate Exposure and Cerebral Amyloid Accumulation: Mechanistic Evaluations in APP/PS1 Mice.Environmental health perspectives · 2024Article
- Nose-to-Brain (N2B) Delivery: An Alternative Route for the Delivery of Biologics in the Management and Treatment of Central Nervous System Disorders.Pharmaceutics · 2023Review
- Nogo-A antibody delivery through the olfactory mucosa mitigates experimental autoimmune encephalomyelitis in the mouse CNS.Cell death discovery · 2023Article
- Recent Trends in Active and Passive Immunotherapies of Alzheimer's Disease.Antibodies (Basel, Switzerland) · 2023Review
- Intranasal delivery of full-length anti-Nogo-A antibody: A potential alternative route for therapeutic antibodies to central nervous system targets.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Proteinopathies: Deciphering Physiology and Mechanisms to Develop Effective Therapies for Neurodegenerative Diseases.Molecular neurobiology · 2022Review
- Intranasal neprilysin rapidly eliminates amyloid-beta plaques, but causes plaque compensations: the explanation why the amyloid-beta cascade may fail?Neural regeneration research · 2022Review
- Therapeutic antibodies - natural and pathological barriers and strategies to overcome them.Pharmacology & therapeutics · 2022Review
- Glial Cell-Based Vascular Mechanisms and Transplantation Therapies in Brain Vessel and Neurodegenerative Diseases.Frontiers in cellular neuroscience · 2021Review
- Neuronally expressed anti-tau scFv prevents tauopathy-induced phenotypes in Drosophila models.Neurobiology of disease · 2020Review
- Passive Immunotherapies for Central Nervous System Disorders: Current Delivery Challenges and New Approaches.Bioconjugate chemistry · 2018Review
- Delivery of immunoglobulin G antibodies to the rat nervous system following intranasal administration: Distribution, dose-response, and mechanisms of delivery.Journal of controlled release : official journal of the Controlled Release Society · 2018Article
- A Novel scFv Anti-Aβ Antibody Reduces Pathological Impairments in APP/PS1 Transgenic Mice via Modulation of Inflammatory Cytokines and Aβ-related Enzymes.Journal of molecular neuroscience : MN · 2018Article
- Combined effects of scanning ultrasound and a tau-specific single chain antibody in a tau transgenic mouse model.Brain : a journal of neurology · 2017Article
- Recombinant Antibody Fragments for Neurodegenerative Diseases.Current neuropharmacology · 2017Review
- High-affinity Anticalins with aggregation-blocking activity directed against the Alzheimer β-amyloid peptide.The Biochemical journal · 2016Article
- Functional Characteristics and Molecular Mechanism of a New scFv Antibody Against Aβ42 Oligomers and Immature Protofibrils.Molecular neurobiology · 2015Article
- Oral delivery of Lactococcus lactis that secretes bioactive heme oxygenase-1 alleviates development of acute colitis in mice.Microbial cell factories · 2015Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amyloid-beta peptide (Aβ)-directed active and passive immunization therapeutic strategies reduce brain levels of Aβ, decrease the severity of beta-amyloid plaque pathology and reverse cognitive deficits in mouse models of Alzheimer's disease (AD). As an alternative approach to passive immunization with full IgG molecules, single-chain variable fragment (scFv) antibodies can modulate or neutralize Aβ-related neurotoxicity and inhibit its aggregation in vitro. In this study, we characterized a scFv derived from a full IgG antibody raised against the C-terminus of Aβ, and studied its passage into the brains of APP transgenic mice, as well as its potential to reduce Aβ-related pathology. We found that the scFv entered the brain after intranasal application, and that it bound to beta-amyloid plaques in the cortex and hippocampus of APP transgenic mice. Moreover, the scFv inhibited Aβ fibril formation and Aβ-mediated neurotoxicity in vitro. In a preventative therapeutic approach chronic intranasal treatment with scFv reduced congophilic amyloid angiopathy (CAA) and beta-amyloid plaque numbers in the cortex of APPswe/PS1dE9 mice. This reduction of CAA and plaque pathology was associated with a redistribution of brain Aβ from the insoluble fraction to the soluble peptide pool. Due to their lack of the effector domain of full IgG, scFv may represent an alternative tool for the treatment of Aβ-related pathology without triggering Fc-mediated effector functions. Additionally, our observations support the possibility that Aβ-directed immunotherapy can reduce Aβ deposition in brain vessels in transgenic mice.
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