Cited by 175Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Efficacy and safety of immunization with phosphorylated tau against neurofibrillary tangles in mice

Boimel, Moran, Grigoriadis, Nikolaos, Lourbopoulos, Athanasios, Haber, Esther, Abramsky, Oded, Rosenmann, Hanna·2010·Experimental Neurology

Abstract

As an abnormally folded and aggregated protein, tau composed of neurofibrillary tangles (NFTs) in Alzheimer's disease and other tauopathies seems to be a candidate for immunotherapy. Yet, the encephalitogenicity of full-length tau protein, recently reported by us in immunized mice, demands to carefully and selectively target pathological tau and address both efficacy (anti-NFT effect) and safety (free of encephalitis). We immunized NFT mice with NFT-related phosphorylated (phos) tau peptides, using an immunization protocol aimed to predispose a proinflammatory milieu in CNS as a set up to detect biohazard, an approach we used when the neurotoxicity of full-length tau was detected [use of complete Freund adjuvant (CFA) with pertussis toxin (PT)]. A decrease of about 40% in NFT burden in CNS was demonstrated and was accompanied with an increase in microglial burden. Anti-phos-tau antibodies were detected in serum and blood vessels in the CNS, while no encephalitogenicity (free of clinical neurological deficits, of adverse effects on brain inflammatory cells and of axonal damage) was recorded. The level of the lysosomal proteases, cathepsins D and L, was affected in the immunized mice suggesting the possible involvement of the lysosomal system in the decrease of NFTs. The robust anti-NFT effect and the lack of encephalitogenicity in NFT mice immunized with phos-tau peptides, even though CFA with PT was included in vaccine, point to their anti-NFT therapeutic potential.

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Crossref · 10.1016/j.expneurol.2010.05.010

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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 [194]

  • Similar tau immunogens administered with a milder adjuvant or fewer immunizations do not produce such adverse reactions.

    “Similar tau immunogens administered with a milder adjuvant or fewer immunizations do not produce such adverse reactions194,196”

    From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [194]

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Authors
Boimel, M., Grigoriadis, N., Lourbopoulos, A., Haber, E., Abramsky, O., & Rosenmann, H.
Affiliations
  • Hebrew University of Jerusalem (IL)
  • AHEPA University Hospital (GR)
Corresponding author
Rosenmann, Hanna
Venue
Experimental Neurology
Publisher
Elsevier BV
Published
2010-08
Volume
224
Issue
2
Pages
472-485
ISSN
0014-4886 (ISSN-L)
OpenAlex
W2091935655
Cited by
174
References
41
Citations by year
2026: 1 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 4 · 2020: 8 · 2019: 10 · 2018: 11 · 2017: 15 · 2016: 8 · 2015: 19 · 2014: 32 · 2013: 23 · 2012: 15
FWCI
12.56
Type
journal article
Language
en
Update notices
erratum (2013-09-01)
Open access
closed
Locations
  • Experimental Neurology (publishedVersion)
  • PubMed (publishedVersion)
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
phosphorylated tau, neurofibrillary tangles, tau immunotherapy, Alzheimer's disease, tauopathy, encephalitogenicity, microglia, lysosomal proteases, anti-tau antibodies, pertussis toxin, complete Freund's adjuvant, neuroinflammation
MeSH terms
Animals, Antibodies, Astrocytes, Brain, Cathepsin D, Encephalitis, Female, Immunization, Lysosomes, Mice, Transgenic, Neurons, Peptide Fragments, Peptide Hydrolases, Phosphoproteins, Vaccines, Synthetic, Neurofibrillary Tangles, tau Proteins, Microglia, Tauopathies, Mice, Cathepsin L

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