Geon Modeling Alzheimer's Disease:
The Artifact of APP and Presenilin Overexpression



In the transgenic mouse model that overexpresses amyloid precursor protein (APP) and presenilin (PS), both amyloid beta peptide (Aβ) and APP intracellular domain (AICD) are elevated. The pathological features, such as hyperexcitability and synaptic dysfunction, were commonly attributed to Aβ, but recent studies suggest that AICD could also make an important contribution. Furthermore, mice overexpressing APP/PS failed to recapitulate a hallmark of Alzheimer's disease: neurofibrillary tangles (NFT). Recently, this feature has been reproduced by a new modeling system called 3D cell culture. It turns out that the key event that enables 3D cell culture to produce robust NFT is elevated 4-repeat (4R) Tau (D'Avanzo et al., 2015). This finding supports the hypothesis that Tau pathology is caused mainly by Tau-mediated hyperexcitability (Paper 6), resulting from elevated 4R Tau (Paper 2).


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