Age-dependent impairment of cognitive and synaptic function in the htau mouse model of Tau pathology

Manuela Polydoro, Christopher M. Acker, Karen Duff, Pablo E. Castillo, Peter Davies

Research output: Contribution to journalArticle

177 Citations (Scopus)

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,weperformed 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.

Original languageEnglish (US)
Pages (from-to)10741-10749
Number of pages9
JournalJournal of Neuroscience
Volume29
Issue number34
DOIs
StatePublished - Aug 26 2009

Fingerprint

Cognition
Neurofibrillary Tangles
Pathology
Memory Disorders
Synaptic Transmission
Hippocampal CA1 Region
Neuronal Plasticity
Long-Term Potentiation
Prosencephalon
Dementia
Alzheimer Disease
Learning
Water
Recognition (Psychology)

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Age-dependent impairment of cognitive and synaptic function in the htau mouse model of Tau pathology. / Polydoro, Manuela; Acker, Christopher M.; Duff, Karen; Castillo, Pablo E.; Davies, Peter.

In: Journal of Neuroscience, Vol. 29, No. 34, 26.08.2009, p. 10741-10749.

Research output: Contribution to journalArticle

Polydoro, Manuela ; Acker, Christopher M. ; Duff, Karen ; Castillo, Pablo E. ; Davies, Peter. / Age-dependent impairment of cognitive and synaptic function in the htau mouse model of Tau pathology. In: Journal of Neuroscience. 2009 ; Vol. 29, No. 34. pp. 10741-10749.
@article{0e0f157ee4144ce8ae9b371c3fddb79f,
title = "Age-dependent impairment of cognitive and synaptic function in the htau mouse model of Tau pathology",
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,weperformed 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.",
author = "Manuela Polydoro and Acker, {Christopher M.} and Karen Duff and Castillo, {Pablo E.} and Peter Davies",
year = "2009",
month = "8",
day = "26",
doi = "10.1523/JNEUROSCI.1065-09.2009",
language = "English (US)",
volume = "29",
pages = "10741--10749",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "34",

}

TY - JOUR

T1 - Age-dependent impairment of cognitive and synaptic function in the htau mouse model of Tau pathology

AU - Polydoro, Manuela

AU - Acker, Christopher M.

AU - Duff, Karen

AU - Castillo, Pablo E.

AU - Davies, Peter

PY - 2009/8/26

Y1 - 2009/8/26

N2 - 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,weperformed 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.

AB - 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,weperformed 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.

UR - http://www.scopus.com/inward/record.url?scp=69449093036&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=69449093036&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.1065-09.2009

DO - 10.1523/JNEUROSCI.1065-09.2009

M3 - Article

VL - 29

SP - 10741

EP - 10749

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 34

ER -