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Cited by 48Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Tauopathy contributes to synaptic and cognitive deficits in a murine model for Alzheimer’s disease

Stancu, Ilie‐Cosmin, Ris, Laurence, Vasconcelos, Bruno, Marinangeli, Claudia, Goeminne, Léonie, Laporte, Vincent, Haylani, Laetitia E., Couturier, Julien +6 more·2014·The FASEB Journal
DOI 10.1096/fj.13-246702
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Abstract

Tau alterations are now considered an executor of neuronal demise and cognitive dysfunction in Alzheimer's disease (AD). Mouse models combining amyloidosis and tauopathy and their parental counterparts are important tools to further investigate the interplay of abnormal amyloid-β (Aβ) and Tau species in pathogenesis, synaptic and neuronal dysfunction, and cognitive decline. Here, we crossed APP/PS1 mice with 5 early-onset familial AD mutations (5xFAD) and TauP301S (PS19) transgenic mice, denoted F(+)/T(+) mice, and phenotypically compared them to their respective parental strains, denoted F(+)/T(-) and F(-)/T(+) respectively, as controls. We found dramatically aggravated tauopathy (~10-fold) in F(+)/T(+) mice compared to the parental F(-)/T(+) mice. In contrast, amyloidosis was unaltered compared to the parental F(+)/T(-) mice. Tauopathy was invariably and very robustly aggravated in hippocampal and cortical brain regions. Most important, F(+)/T(+) displayed aggravated cognitive deficits in a hippocampus-dependent spatial navigation task, compared to the parental F(+)/T(-) strain, while parental F(-)/T(+) mice did not display cognitive impairment. Basal synaptic transmission was impaired in F(+)/T(+) mice compared to nontransgenic mice and the parental strains (≥40%). Finally, F(+)/T(+) mice displayed a significant hippocampal atrophy (~20%) compared to nontransgenic mice, in contrast to the parental strains. Our data indicate for the first time that pathological Aβ species (or APP/PS1) induced changes in Tau contribute to cognitive deficits correlating with synaptic deficits and hippocampal atrophy in an AD model. Our data lend support to the amyloid cascade hypothesis with a role of pathological Aβ species as initiator and pathological Tau species as executor.

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Crossref · 10.1096/fj.13-246702

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  • In 5xFAD/PS19 mice, co-expression of Tau led to deficits in basal synaptic transmission, spatial memory deficits, increased neuroinflammation, robust hippocampal atrophy, and severe loss of neurons in the hippocampal CA1 layer.

    “Co-expression of Tau lead to deficits in basal synaptic transmission, as well as spatial memory deficits [57] and increased neuroinflammation [56]. Of note, 5xFAD/PS19 mice presented with robust hippocampal atrophy and severe loss of neurons in the hippocampal CA1 layer [56,57].”

    From Neuron Loss in Alzheimer’s Disease: Translation in Transgenic Mouse Models (2020) · cites this paper as [57]

  • Synaptic dysfunction is a hallmark of AD and has been reported in both combined pathology mouse models and human AD brains.

    “Synaptic dysfunction is a hallmark of AD and has been reported in both combined pathology mouse models and human AD brains. 43 , 58 , 59”

    From Unique transcriptomic alterations in 5XFAD;PS19 mouse model identify glial lipid dysregulation and coordinated microglial–oligodendrocyte responses (2026) · cites this paper as [58]

  • Crossing transgenic APP mouse over-expression models with tau mouse models generally shows that Aβ accelerates tau pathology.

    “The results generally show that Aβ accelerates tau pathology (Chabrier et al., 2014; Heraud et al., 2014; Stancu et al., 2014; Chen et al., 2016).”

    From β-amyloid accumulation enhances microtubule associated protein tau pathology in an APPNL-G-F/MAPTP301S mouse model of Alzheimer’s disease (2024) · cites this paper as Stancu et al., 2014

  • Findings in models harboring transgenic Aβ peptides in the absence of APP overexpression strikingly contrast the obvious exacerbation of tau pathology observed in tau transgenic mice when crossed with mouse models of AD overexpressing mutant APP.

    “These findings in models harboring transgenic Aβ peptides in the absence of APP overexpression strikingly contrast the obvious exacerbation of tau pathology observed in tau transgenic mice when crossed with mouse models of AD overexpressing mutant APP [7,8,9,10,11,12,13,36].”

    From Characterization of a Mouse Model of Alzheimer’s Disease Expressing Aβ4-42 and Human Mutant Tau (2021) · cites this paper as [10]

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Authors
Stancu, I., Ris, L., Vasconcelos, B., Marinangeli, C., Goeminne, L., Laporte, V., Haylani, L. E., Couturier, J., Schakman, O., Gailly, P., Pierrot, N., Kienlen‐Campard, P., Octave, J., & Dewachter, I.
Affiliations
  • UCLouvain (BE)
  • University of Mons (BE)
Corresponding author
Dewachter, Ilse
ORCID
Venue
The FASEB Journal
Publisher
Wiley
Published
2014-03-06
Volume
28
Issue
6
Pages
2620-2631
ISSN
  • 0892-6638 (ISSN-L)
  • 1530-6860
DOI
10.1096/fj.13-246702
OpenAlex
W2152709750
Cited by
48
References
47
Citations by year
2025: 6 · 2024: 2 · 2023: 2 · 2022: 6 · 2021: 5 · 2020: 2 · 2019: 1 · 2018: 4 · 2017: 4 · 2016: 8 · 2015: 6 · 2014: 2
FWCI
3.89
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • The FASEB Journal (publishedVersion)
  • PubMed (publishedVersion)
  • DIAL (Catholic University of Leuven) (submittedVersion)
  • Document Server@UHasselt (UHasselt) (submittedVersion)
  • ORBi UMONS (submittedVersion)
Funders
Internationale Stichting Alzheimer Onderzoek
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, Alzheimer's disease, amyloid-beta, APP/PS1 mice, synaptic transmission, cognitive impairment, hippocampal atrophy, amyloid hypothesis, spatial navigation, hippocampal-dependent memory
MeSH terms
Alzheimer Disease, Animals, Atrophy, Cognition Disorders, Disease Models, Animal, Female, Hippocampus, Humans, Male, Mice, Transgenic, Synaptic Transmission, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, tau Proteins, Maze Learning, Tauopathies, Glycogen Synthase Kinase 3, JNK Mitogen-Activated Protein Kinases, Mice, Presenilin-1

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