ArticleActa neuropathologica2018
Selective targeting of 3 repeat Tau with brain penetrating single chain antibodies for the treatment of neurodegenerative disorders.
Article in Acta neuropathologica, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
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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
17 citing papers in PubMed, 27 citations in OpenAlex.
- Bioconjugates for improved delivery of oligonucleotide therapeutics to the central nervous system.Advanced drug delivery reviews · 2026Review
- AAV-mediated peripheral scFv's administration to reduce cerebral tau in adult P301S transgenic mice: Mono-vs. combination therapy.Molecular therapy. Methods & clinical development · 2025Article
- Recombinant Antibody Fragments for Neurological Disorders: An Update.Current neuropharmacology · 2024Review
- Tau-targeting therapies for Alzheimer disease: current status and future directions.Nature reviews. Neurology · 2023Review
- Article
- Immunogenicity of MultiTEP platform technology-based Tau vaccine in non-human primates.NPJ vaccines · 2022Article
- Inhibition of Tau seeding by targeting Tau nucleation core within neurons with a single domain antibody fragment.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Novel Brain-Penetrating Single Chain Antibodies Directed Against 3RTau for the Treatment of Alzheimer's Disease and Related Dementias.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Review
- Mutant three-repeat tau expression initiates retinal ganglion cell death through Caspase-2.Neurobiology of disease · 2021Article
- Recent advances in tau-directed immunotherapy against Alzheimer's disease: an overview of pre-clinical and clinical development.Metabolic brain disease · 2020Review
- Tau immunotherapies: Lessons learned, current status and future considerations.Neuropharmacology · 2020Review
- Intramuscular injection of vectorized-scFvMC1 reduces pathological tau in two different tau transgenic models.Acta neuropathologica communications · 2020Article
- Fibrillar form of α-synuclein-specific scFv antibody inhibits α-synuclein seeds induced aggregation and toxicity.Scientific reports · 2020Article
- Neuronally expressed anti-tau scFv prevents tauopathy-induced phenotypes in Drosophila models.Neurobiology of disease · 2020Review
- Intersection of pathological tau and microglia at the synapse.Acta neuropathologica communications · 2019Review
- Systemic peptide mediated delivery of an siRNA targeting α-syn in the CNS ameliorates the neurodegenerative process in a transgenic model of Lewy body disease.Neurobiology of disease · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Alzheimer's disease (AD) is the most common form of dementia in the elderly affecting more than 5 million people in the U.S. AD is characterized by the accumulation of β-amyloid (Aβ) and Tau in the brain, and is manifested by severe impairments in memory and cognition. Therefore, removing tau pathology has become one of the main therapeutic goals for the treatment of AD. Tau (tubulin-associated unit) is a major neuronal cytoskeletal protein found in the CNS encoded by the gene MAPT. Alternative splicing generates two major isoforms of tau containing either 3 or 4 repeat (R) segments. These 3R or 4RTau species are differentially expressed in neurodegenerative diseases. Previous studies have been focused on reducing Tau accumulation with antibodies against total Tau, 4RTau or phosphorylated isoforms. Here, we developed a brain penetrating, single chain antibody that specifically recognizes a pathogenic 3RTau. This single chain antibody was modified by the addition of a fragment of the apoB protein to facilitate trafficking into the brain, once in the CNS these antibody fragments reduced the accumulation of 3RTau and related deficits in a transgenic mouse model of tauopathy. NMR studies showed that the single chain antibody recognized an epitope at aa 40-62 of 3RTau. This single chain antibody reduced 3RTau transmission and facilitated the clearance of Tau via the endosomal-lysosomal pathway. Together, these results suggest that targeting 3RTau with highly specific, brain penetrating, single chain antibodies might be of potential value for the treatment of tauopathies such as Pick'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.