Cited by 331Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroscience and Neuropharmacology Research

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Age-Dependent Impairment of Cognitive and Synaptic Function in the htau Mouse Model of Tau Pathology

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Polydoro, Manuela, Acker, Christopher M., Duff, Karen, Castillo, Pablo E., Davies, Peter·2009·The Journal of Neuroscience

DOI 10.1523/jneurosci.1065-09.2009PMC PMC2760256

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Abstract

A hallmark feature of Alzheimer's disease pathology is the presence of neurofibrillary tangles (NFTs), which are intracellular aggregates of conformationally abnormal and hyperphosphorylated tau. The presence of NFTs in the forebrain is associated with impairments of cognitive function, supporting a central role for tau in dementia. The significance of the accumulation of NFTs for neuronal and cognitive function is still obscure. It is possible that NFTs disrupt synaptic transmission and plasticity, leading to memory deficits and cognitive malfunction. To elucidate the relationship between the development of tau pathology and synaptic and cognitive functions, we performed behavioral tests and electrophysiological experiments in the htau mouse. Here we report age-dependent cognitive and physiological impairments in htau mice that preceded neurodegeneration. Twelve-month-old htau mice with moderate tau pathology, but not 4-month-old mice with early-stage tau pathology, presented cognitive deficits in an object recognition memory task in which the visual recognition memory of a novel object was disrupted. Moreover, only 12-month-old htau mice exhibit spatial memory deficits, as indicated by the impaired performance in the Morris water maze. In addition, we report that basal synaptic transmission and induction of long-term potentiation with high-frequency stimulation, but not theta burst stimulation, is perturbed in hippocampal CA1 region of old but not young htau mice. Our results suggest that tau pathology may underlie an age-dependent learning impairment through disruption of synaptic function.

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Authors: Polydoro, M., Acker, C. M., Duff, K., Castillo, P. E., & Davies, P.
Affiliations: Albert Einstein College of Medicine (US)
Columbia University (US)
ORCID: Polydoro, Manuela
Duff, Karen
Castillo, Pablo E.
Davies, Peter
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2009-08-26
Volume: 29
Issue: 34
Pages: 10741-10749
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.1065-09.2009
PMC: PMC2760256
OpenAlex: W2048865592
Cited by: 329
References: 34
Citations by year: 2026: 7 · 2025: 17 · 2024: 13 · 2023: 22 · 2022: 20 · 2021: 23 · 2020: 24 · 2019: 15 · 2018: 26 · 2017: 19 · 2016: 18 · 2015: 24 · 2014: 25 · 2013: 20 · 2012: 17
FWCI: 12.41
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 184 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Aging (R01AG022102)
National Institute of Neurological Disorders and Stroke (P01NS048447, NS048447)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: tau pathology, Alzheimer's disease, neurofibrillary tangles, cognitive impairment, object recognition memory, spatial memory, synaptic transmission, long-term potentiation, theta burst stimulation, hippocampal CA1, synaptic plasticity
MeSH terms: Age Factors, Aging, Analysis of Variance, Animals, Cognition Disorders, Disease Models, Animal, Electric Stimulation, Exploratory Behavior, Hippocampus, Mice, Inbred C57BL, Neuropsychological Tests, Synapses, Neurofibrillary Tangles, tau Proteins, Long-Term Potentiation, Pyramidal Cells, Mice, Knockout, Maze Learning, Excitatory Postsynaptic Potentials, Recognition, Psychology, Tauopathies, Mice, Dual Specificity Phosphatase 2, In Vitro Techniques

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Age-Dependent Impairment of Cognitive and Synaptic Function in the htau Mouse Model of Tau Pathology

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