Cited by 196Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Targeting Phospho-Ser422 by Active Tau Immunotherapy in the THYTau22 Mouse Model: A Suitable Therapeutic Approach

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Nadege Zommer, Nicolas Sergeant, Susanna Schraen-Maschke, David Blum, Luc Buee·2012·Current Alzheimer Research

Abstract

Recent data indicate that Tau immunotherapy may be relevant for interfering with neurofibrillary degeneration in Alzheimer disease and related disorders referred to as Tauopathies. The key question for immunotherapy is the choice of the epitope to target. Abnormal phosphorylation is a well-described post-translational modification of Tau proteins and may be a good target. In the present study, we investigated the effects of active immunization against the pathological epitope phospho-Ser422 in the THY-Tau22 transgenic mouse model. Starting from 3-6 months of age, THY-Tau22 mice develop hippocampal neurofibrillary tangle-like inclusions and exhibit phosphorylation of Tau on several AD-relevant Tau epitopes. Three month-old THY-Tau22 mice were immunized with a peptide including the phosphoserine 422 residue while control mice received the adjuvant alone. A specific antibody response against the phospho-Ser422 epitope was observed. We noticed a decrease in insoluble Tau species (AT100- and pS422 immunoreactive) by both biochemical and immunohistochemical means correlated with a significant cognitive improvement using the Y-maze. This Tau immunotherapy may facilitate Tau clearance from the brain toward the periphery since, following immunization, an increase in Tau concentrations was observed in blood. Overall, the present work is, to our knowledge, the first one to demonstrate that active immunotherapy targeting a real pathological epitope such as phospho-Ser422 epitope is efficient. This immunotherapy allows for Tau clearance and improves cognitive deficits promoted by Tau pathology in a well-defined Tau transgenic model.

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Crossref · 10.2174/156720512800492503

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  • Active tau immunization reduces tau pathology by targeting single or multiple phospho-epitopes, the amino terminus, full-length normal and mutant tau, or aggregated tau.

    “Active tau immunization has been shown to reduce tau pathology by targeting single185, 187, 189–193 or multiple194 phospho-epitopes, the amino terminus195, full-length normal and mutant tau196, 197, or aggregated tau198.”

    From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [192]

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Authors
Zommer, N., Sergeant, N., Schraen-Maschke, S., Blum, D., & Buee, L.
Affiliations
  • Inserm UMR837, Alzheimer&Tauopathies, Centre de Recherches Jean-Pierre Aubert, Faculte de Médecine Pole Recherche, Place de Verdun, F-59045 Lille, France.
  • Inserm (FR)
Venue
Current Alzheimer Research
Published
2012-04-26
Volume
9
Issue
4
Pages
397-405
ISSN
1567-2050 (ISSN-L)
OpenAlex
W2130365060
Cited by
193
References
49
Citations by year
2026: 2 · 2025: 7 · 2024: 9 · 2023: 8 · 2022: 8 · 2021: 3 · 2020: 12 · 2019: 18 · 2018: 14 · 2017: 17 · 2016: 13 · 2015: 21 · 2014: 34 · 2013: 22 · 2012: 5
FWCI
17.80
Type
journal article
Language
en
Open access
Locations
  • Current Alzheimer Research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
Institut National de la Santé et de la Recherche Médicale
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
tau immunotherapy, active immunization, tauopathy, Alzheimer's disease, neurofibrillary tangles, tau phosphorylation, peptide immunization, cognitive impairment, tau clearance, transgenic mice
MeSH terms
Age Factors, Alzheimer Disease, Animals, Antibodies, Cognition Disorders, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Hippocampus, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Peptides, Phosphorylation, Serine, Immunotherapy, Active, tau Proteins, Maze Learning, Mice

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