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

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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

DOI 10.2174/156720512800492503PMC PMC3637173

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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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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)
ORCID: Nicolas Sergeant
David Blum
Venue: Current Alzheimer Research
Publisher: Bentham Science Publishers Ltd.
Published: 2012-04-26
Volume: 9
Issue: 4
Pages: 397-405
ISSN: 1567-2050 (ISSN-L)
DOI: 10.2174/156720512800492503
PMC: PMC3637173
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: green
www.ncbi.nlm.nih.gov
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: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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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Targeting Phospho-Ser422 by Active Tau Immunotherapy in the THYTau22 Mouse Model: A Suitable Therapeutic Approach

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