ArticleJournal of neural transmission (Vienna, Austria : 1996)2015
Passive immunization targeting the N-terminal projection domain of tau decreases tau pathology and improves cognition in a transgenic mouse model of Alzheimer disease and tauopathies.
Article in Journal of neural transmission (Vienna, Austria : 1996), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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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.
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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
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Cognitive Decline in Preclinical Alzheimer's Disease: Amyloid-Beta versus Tauopathy.Journal of Alzheimer's disease : JAD · 2018Pooled it
- Tau physiology and pathology: impacts on cellular structures and neurodegenerative diseases.Inflammopharmacology · 2026Review
- Immunization targeting diseased proteins in synucleinopathy and tauopathy: insights from clinical trials.Translational neurodegeneration · 2025Review
- Acute targeting of N-terminal tau protein has long-lasting beneficial effects in Tg2576 APP/Aβ mouse model by reducing cognitive impairment, cerebral Aβ-amyloidosis, synaptic remodeling and microgliosis later in life.Acta neuropathologica communications · 2025Article
- Immunotherapies: A Treasure Trove of Alzheimer's Disease.Current pharmaceutical biotechnology · 2025Review
- New progress on the role and mechanism of tau protein in Alzheimer's disease and depression.Frontiers in neurology · 2025Review
- Targeting Protein Misfolding and Aggregation as a Therapeutic Perspective in Neurodegenerative Disorders.International journal of molecular sciences · 2024Review
- Potential Mechanisms of Tunneling Nanotube Formation and Their Role in Pathology Spread in Alzheimer's Disease and Other Proteinopathies.International journal of molecular sciences · 2024Review
- Nanoscale imaging of pT217-tau in aged rhesus macaque entorhinal and dorsolateral prefrontal cortex: Evidence of interneuronal trafficking and early-stage neurodegeneration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Tau and Alzheimer's disease: Past, present and future.Cytoskeleton (Hoboken, N.J.) · 2024Review
- New Approaches to the Treatment of Frontotemporal Dementia.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Gut-brain connections in neurodegenerative disease: immunotherapeutic targeting of Bin1 in inflammatory bowel disease and Alzheimer's disease.Frontiers in pharmacology · 2023Review
- Towards a Mechanistic Model of Tau-Mediated Pathology in Tauopathies: What Can We Learn from Cell-Based In Vitro Assays?International journal of molecular sciences · 2022Review
- Targeting tau only extracellularly is likely to be less efficacious than targeting it both intra- and extracellularly.Seminars in cell & developmental biology · 2022Review
- Therapeutic strategies for tauopathies and drug repurposing as a potential approach.Biochemical pharmacology · 2022Review
- Aducanumab and Its Effects on Tau Pathology: Is This the Turning Point of Amyloid Hypothesis?International journal of molecular sciences · 2022Review
- Research Progress of Nanomaterial Mechanics for Targeted Treatment of Muscle Strains in Sports Rehabilitation Training.Applied bionics and biomechanics · 2022Article
- Review
- Tau Seeding Mouse Models with Patient Brain-Derived Aggregates.International journal of molecular sciences · 2021Review
- Hypothesis: Tau pathology is an initiating factor in sporadic Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2021Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intraneuronal accumulation of abnormally hyperphosphorylated tau in the brain is a histopathological hallmark of Alzheimer's disease and a family of related neurodegenerative disorders collectively called tauopathies. At present there is no effective treatment available for these progressive neurodegenerative diseases which are clinically characterized by dementia in mid to old-age. Here we report the treatment of 14-17-months-old 3xTg-AD mice with tau antibodies 43D (tau 6-18) and 77E9 (tau 184-195) to the N-terminal projection domain of tau or mouse IgG as a control by intraperitoneal injection once a week for 4 weeks, and the effects of the passive immunization on reduction of hyperphosphorylated tau, Aβ accumulation and cognitive performance in these animals. We found that treatment with tau antibodies 43D and 77E9 reduced total tau level, decreased tau hyperphosphorylated at Ser199, Ser202/Thr205 (AT8), Thr205, Ser262/356 (12E8), and Ser396/404 (PHF-1) sites, and a trend to reduce Aβ pathology. Most importantly, targeting N-terminal tau especially by 43D (tau 6-18) improved reference memory in the Morris water maze task in 3xTg-AD mice. We did not observe any abnormality in general physical characteristics of the treated animals with either of the two antibodies during the course of this study. Taken together, our studies demonstrate for the first time (1) that passive immunization targeting normal tau can effectively clear the hyperphosphorylated protein and possibly reduce Aβ pathology from the brain and (2) that targeting N-terminal projection domain of tau containing amino acid 6-18 is especially beneficial. Thus, targeting selective epitopes of N-terminal domain of tau may present a novel effective therapeutic opportunity for Alzheimer disease and other tauopathies.
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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.