The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Efficacy and safety of immunization with phosphorylated tau against neurofibrillary tangles in mice
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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“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]
In the citing paper
“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]
Citations
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Research works printed but not linked: 2
- Boimel, 2006, Inflammation in the CNS increases Alzheimer's disease related neurofibrillary tangle burden: a study of experimental autoimmune encephalomyelitis in a transgenic animal model for neurofibrillary tangles, Neurology, 66, 279
- Lourbopoulos, 2007, Modified Bielschowsky silver impregnation combined with hematoxylin or cresyl violet counterstaining as a potential tool for the simultaneous study of inflammation and axonal injury in the central nervous system, Aristotle Univer. Med. J., 34, 31
Cited by
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Tau pathology and neurodegeneration
Spillantini, M. G., & Goedert, M. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70090-5 · Cited by 1,133
Tau-targeting therapies for Alzheimer disease
Congdon, E. E., & Sigurdsson, E. M. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0013-z · Cited by 1,113
Morris, M., Maeda, S., Vossel, K., & Mucke, L. (2011) · Neuron · doi:10.1016/j.neuron.2011.04.009 · Cited by 899
Therapeutics of Alzheimer's disease: Past, present and future
Anand, R., Gill, K. D., & Mahdi, A. A. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.07.004 · Cited by 765
Yanamandra, K., Kfoury, N., Jiang, H., Mahan, T. E., Ma, S., Maloney, S. E., Wozniak, D. F., Diamond, M. I., & Holtzman, D. M. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.046 · Cited by 574
Metadata
- 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
- 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
- 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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