Tau- But not Aß -pathology enhances NMDAR-dependent depotentiation in AD-mouse models

Enrico Faldini, Tariq Ahmed, Luc Bueé, David Blum, Detlef Balschun

Research output: Contribution to journalArticle

Abstract

Many mouse models of Alzheimer's disease (AD) exhibit impairments in hippocampal long-term-potentiation (LTP), seemingly corroborating the strong correlation between synaptic loss and cognitive decline reported in human studies. In other AD mouse models LTP is unaffected, but other defects in synaptic plasticity may still be present. We recently reported that THY-Tau22 transgenic mice, that overexpress human Tau protein carrying P301S and G272 V mutations and show normal LTP upon high-frequency-stimulation (HFS), develop severe changes in NMDAR mediated long-term-depression (LTD), the physiological counterpart of LTP. In the present study, we focused on putative effects of AD-related pathologies on depotentiation (DP), another form of synaptic plasticity. Using a novel protocol to induce DP in the CA1-region, we found in 11-15 months old male THY-Tau22 and APPPS1-21 transgenic mice that DP was not deteriorated by Aß pathology while significantly compromised by Tau pathology. Our findings advocate DP as a complementary form of synaptic plasticity that may help in elucidating synaptic pathomechanisms associated with different types of dementia.

Original languageEnglish
Article number202
JournalActa Neuropathologica Communications
Volume7
Issue number1
DOIs
Publication statusPublished - 9 Dec 2019

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Long-Term Synaptic Depression
Long-Term Potentiation
Alzheimer Disease
Neuronal Plasticity
Pathology
Transgenic Mice
Dementia
Mutation

Keywords

  • Alzheimer's disease
  • CA1-region
  • Depotentiation
  • Glycogen synthase kinase-3β
  • Hippocampus
  • Synaptic plasticity
  • Tau

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Tau- But not Aß -pathology enhances NMDAR-dependent depotentiation in AD-mouse models. / Faldini, Enrico; Ahmed, Tariq; Bueé, Luc; Blum, David; Balschun, Detlef.

In: Acta Neuropathologica Communications, Vol. 7, No. 1, 202, 09.12.2019.

Research output: Contribution to journalArticle

Faldini, Enrico ; Ahmed, Tariq ; Bueé, Luc ; Blum, David ; Balschun, Detlef. / Tau- But not Aß -pathology enhances NMDAR-dependent depotentiation in AD-mouse models. In: Acta Neuropathologica Communications. 2019 ; Vol. 7, No. 1.
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