Geon Alzheimer's Disease: The Role of AICD and Aβ in Excitability

 

Abstract

In the transgenic mouse models that overexpress amyloid precursor protein (APP) and/or presenilin, neuronal excitability increases at the early stage. Since the overexpression produces higher level of amyloid beta (Aβ) peptides and APP intracellular domain (AICD), the hyperexcitability could arise from AICD and/or Aβ. Their underlying mechanisms are explored in this paper. AICD has been shown to act as a transcription factor, which may regulate the expression of miR-342-5p, the microRNA that suppresses the expression of Ankyrin-G. Hence, higher AICD level is expected to reduce the production of Ankyrin-G, thereby enhancing excitability (see Paper 2). Extracellular Aβ oligomers may facilitate internalization of AMPA receptors, resulting in lower excitability, but the internalized Aβ could activate GSK-3 to enhance excitability. These findings suggest that the early hyperactivity is more likely to arise from AICD than Aβ.

 

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