"The amyloid precursor protein (APP) is central to AD pathogenesis and we recently showed that its intracellular domain (AICD) could modify synaptic signal integration. We now hypothezise that AICD modifies neuron firing activity, thus contributing to the disruption of memory processes. Using cellular, electrophysiological and behavioural techniques, we showed that pathological AICD levels weakens CA1 neuron firing activity through a gene transcription-dependent mechanism. Furthermore, increased AICD production in hippocampal neurons modifies oscillatory activity, specifically in the gamma frequency range, and disrupts spatial memory task. Collectively, our data suggest that AICD pathological levels, observed in AD mouse models and in human patients, might contribute to progressive neuron homeostatic failure, driving the shift from normal ageing to AD."
Model Type: Neuron or other electrically excitable cell
Region(s) or Organism(s): Hippocampus
Cell Type(s): Hippocampus CA1 pyramidal GLU cell
Currents: I Na,t; I A; I K; I M; I h; I L high threshold; I_AHP
Receptors: NMDA
Transmitters: Glutamate
Model Concept(s): Aging/Alzheimer`s; Oscillations; Action Potentials; Memory
Simulation Environment: NEURON
Implementer(s): Bianchi, Daniela [danielabianchi12 -at- gmail.com]
References:
Pousinha PA et al. (2019). The Amyloid Precursor Protein C-Terminal Domain Alters CA1 Neuron Firing, Modifying Hippocampus Oscillations and Impairing Spatial Memory Encoding. Cell reports. 29 [PubMed]