Cited by 214Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Intracerebral injection of preformed synthetic tau fibrils initiates widespread tauopathy and neuronal loss in the brains of tau transgenic mice

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Peeraer, Eve, Bottelbergs, Astrid, Van Kolen, Kristof, Stancu, Ilie-Cosmin, Vasconcelos, Bruno, Mahieu, Michel, Duytschaever, Hilde, Ver Donck, Luc +10 more·2015·Neurobiology of Disease

Abstract

Neurofibrillary tangles composed of hyperphosphorylated fibrillized tau are found in numerous tauopathies including Alzheimer's disease. Increasing evidence suggests that tau pathology can be transmitted from cell-to-cell; however the mechanisms involved in the initiation of tau fibrillization and spreading of disease linked to progression of tau pathology are poorly understood. We show here that intracerebral injections of preformed synthetic tau fibrils into the hippocampus or frontal cortex of young tau transgenic mice expressing mutant human P301L tau induces tau hyperphosphorylation and aggregation around the site of injection, as well as a time-dependent propagation of tau pathology to interconnected brain areas distant from the injection site. Furthermore, we show that the tau pathology as a consequence of injection of tau preformed fibrils into the hippocampus induces selective loss of CA1 neurons. Together, our data confirm previous studies on the seeded induction and the spreading of tau pathology in a different tau transgenic mouse model and reveals neuronal loss associated with seeded tau pathology in tau transgenic mouse brain. These results further validate the utility of the tau seeding model in studying disease transmission, and provide a more complete in vivo tauopathy model with associated neurodegeneration which can be used to investigate the mechanisms involved in tau aggregation and spreading, as well as aid in the search for disease modifying treatments for Alzheimer's disease and related tauopathies.

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Crossref · 10.1016/j.nbd.2014.08.032

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  • Injection in tauP301L transgenic mice results in elevated p-tau levels close to the injection site.

    “Injection in tauP301L transgenic mice resulted in elevated p-tau levels close to the site of injection [143].”
  • The spread of tau pathology is time-dependent from the injection site to distant interconnected brain regions.

    “In addition, the spread of tau pathology is time-dependent from the injection site to distant interconnected brain regions [58].”
  • Intracerebral injection of synthetic tau fibrils into the hippocampus or frontal cortex of tau-P301L transgenic mice at 3 months increases tau hyperphosphorylation and accumulation around the injection site.

    “An in vivo study has demonstrated that the intracerebral injection of synthetic tau fibrils into the hippocampus or frontal cortex of tau-P301L transgenic mice at 3 months increases tau hyperphosphorylation and accumulation around the injection site.”
  • Tau pathology as a consequence of injection with tau-preformed fibrils into the hippocampus of tau-P301L transgenic mice induced selective neuron loss of the CA1 region.

    “Peeraer and colleagues found that the tau pathology as a consequence of injection with tau-preformed fibrils into the hippocampus of tau-P301L transgenic mice induced selective neuron loss of the CA1 region [58].”

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Authors
Peeraer, E., Bottelbergs, A., Van Kolen, K., Stancu, I.-C., Vasconcelos, B., Mahieu, M., Duytschaever, H., Ver Donck, L., Torremans, A., Sluydts, E., Van Acker, N., Kemp, J. A., Mercken, M., Brunden, K. R., Trojanowski, J. Q., Dewachter, I., Lee, V. M. Y., & Moechars, D.
Affiliations
  • Janssen (Belgium) (BE)
  • UCLouvain (BE)
  • HistoGeneX (Belgium) (BE)
  • University of Pennsylvania (US)
Corresponding author
Moechars, Diederik
Venue
Neurobiology of Disease
Publisher
Elsevier BV
Published
2015-01
Volume
73
Pages
83-95
ISSN
0969-9961 (ISSN-L)
OpenAlex
W1979363343
Cited by
214
References
46
Citations by year
2026: 4 · 2025: 15 · 2024: 18 · 2023: 18 · 2022: 21 · 2021: 28 · 2020: 19 · 2019: 25 · 2018: 19 · 2017: 15 · 2016: 18 · 2015: 12 · 2014: 2
FWCI
10.42
Type
journal article
Language
en
Open access
Locations
  • Neurobiology of Disease (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Digital Access to Libraries (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Document Server@UHasselt (UHasselt) (submittedVersion)
Funders
Institute for the Promotion of Innovation by Science and Technology (IWT120492)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
tauopathy, tau fibrils, tau seeding, tau hyperphosphorylation, tau aggregation, neurofibrillary tangles, P301L tau, tau transgenic mice, Alzheimer's disease, disease transmission, neuronal loss, CA1 neurons, hippocampus, frontal cortex
MeSH terms
Age Factors, Analysis of Variance, Animals, Disease Models, Animal, Gene Expression Regulation, Hippocampus, Humans, Functional Laterality, Mice, Transgenic, Mutation, Neurofibrillary Tangles, tau Proteins, Disease Progression, Tauopathies, Mice

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