1) APP carboxy terminal fragments (CTF) are cleaved into cytotoxic peptides

2) APP CTF have important physiological roles
They are directed towards the nucleus, driven by Fe65.

In the nucleus, APP-CTFs activate transcription factors, for the activation of genes (that could be trophic factors or Neprilysin).

Factors involved in the targetting towards nucleus (Pardossi-Picquartd et al, Neuron, Vol. 46, 541–554, May 19, 2005,)

A loss of APP CTFs is observed in AD. It is well correlated with the progression of tau pathology and Abeta deposition. It could be the cause of AD, since these fragments are most likely, directly or indirectly, survival factors. (Sergeant et al, 2002).
In fact, our hypothesis is that Alzheimer 's disease is a true tauopathy stimulated by the lack of trophic factors (loss of APP-CTFs).

 other molecular aspects