ArticleJournal of neuroinflammation2014
Epitope analysis following active immunization with tau proteins reveals immunogens implicated in tau pathogenesis.
Article in Journal of neuroinflammation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Tau-targeting active immunotherapy slows progression and reduces pathology in mouse models of tauopathy.Brain pathology (Zurich, Switzerland) · 2026Article
- Development of an anti-tauopathy mucosal vaccine specifically targeting pathologic conformers.NPJ vaccines · 2024Article
- Proteopathic tau primes and activates interleukin-1β via myeloid-cell-specific MyD88- and NLRP3-ASC-inflammasome pathway.Cell reports · 2021Article
- Recent advances in tau-directed immunotherapy against Alzheimer's disease: an overview of pre-clinical and clinical development.Metabolic brain disease · 2020Review
- Alzheimer's disease: phenotypic approaches using disease models and the targeting of tau protein.Expert opinion on therapeutic targets · 2020Review
- Progressive supranuclear palsy: Advances in diagnosis and management.Parkinsonism & related disorders · 2020Review
- Active immunization with tau epitope in a mouse model of tauopathy induced strong antibody response together with improvement in short memory and pSer396-tau pathology.Neurobiology of disease · 2020Article
- Targeting Tau to Treat Clinical Features of Huntington's Disease.Frontiers in neurology · 2020Review
- Intersection of pathological tau and microglia at the synapse.Acta neuropathologica communications · 2019Review
- Saponins fromMolecules (Basel, Switzerland) · 2019Review
- AD-Related N-Terminal Truncated Tau Is Sufficient to Recapitulate In Vivo the Early Perturbations of Human Neuropathology: Implications for Immunotherapy.Molecular neurobiology · 2018Article
- A Closer Look into the Role of Protein Tau in the Identification of Promising Therapeutic Targets for Alzheimer's Disease.Brain sciences · 2018Review
- Tau-targeting therapies for Alzheimer disease.Nature reviews. Neurology · 2018Review
- Tau and neuroinflammation: What impact for Alzheimer's Disease and Tauopathies?Biomedical journal · 2018Review
- Therapeutic Strategies for Restoring Tau Homeostasis.Cold Spring Harbor perspectives in medicine · 2018Review
- Tau Immunotherapies for Alzheimer's Disease and Related Tauopathies: Progress and Potential Pitfalls.Journal of Alzheimer's disease : JAD · 2018Review
- Prophylactic Active Tau Immunization Leads to Sustained Reduction in Both Tau and Amyloid-β Pathologies in 3xTg Mice.Scientific reports · 2017Article
- Emerging Diagnostic and Therapeutic Strategies for Tauopathies.Current neurology and neuroscience reports · 2017Review
- Friend or foe: the dichotomous impact of T cells on neuro-de/re-generation during aging.Oncotarget · 2017Review
- Internalization of tau antibody and pathological tau protein detected with a flow cytometry multiplexing approach.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2016Article
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundAbnormal tau hyperphosphorylation and its accumulation into intra-neuronal neurofibrillary tangles are linked to neurodegeneration in Alzheimer's disease and similar tauopathies. One strategy to reduce accumulation is through immunization, but the most immunogenic tau epitopes have so far remained unknown. To fill this gap, we immunized mice with recombinant tau to build a map of the most immunogenic tau epitopes.
methodsNon-transgenic and rTg4510 tau transgenic mice aged 5 months were immunized with either human wild-type tau (Wt, 4R0N) or P301L tau (4R0N). Each protein was formulated in Quil A adjuvant. Sera and splenocytes of vaccinated mice were collected to assess the humoral and cellular immune responses to tau. We employed a peptide array assay to identify the most effective epitopes. Brain histology was utilized to measure the effects of vaccination on tau pathology and inflammation.
resultsHumoral immune responses following immunization demonstrated robust antibody titers (up to 1:80,000 endpoint titers) to each tau species in both mice models. The number of IFN-γ producing T cells and their proliferation were also increased in splenocytes from immunized mice, indicating an increased cellular immune response, and tau levels and neuroinflammation were both reduced. We identified five immunogenic motifs within either the N-terminal (9-15 and 21-27 amino acids), proline rich (168-174 and 220-228 amino acids), or the C-terminal regions (427-438 amino acids) of the wild-type and P301L tau protein sequence.
conclusionsOur study identifies five previously unknown immunogenic motifs of wild-type and mutated (P301L) tau protein. Immunization with both proteins resulted in reduced tau pathology and neuroinflammation in a tau transgenic model, supporting the efficacy of tau immunotherapy in tauopathy.
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