Accumulation of carboxy-terminal fragments of APP increases phosphodiesterase 8B.

The long-standing "amyloid hypothesis" that Alzheimer's disease is caused by the production and aggregation of amyloid-β faces serious challenges by data recently obtained from neuroimaging studies and amyloid-β amyloid-focused clinical trials. Meanwhile, accumulation of carboxy-terminal fragments (CTFs) of the amyloid precursor protein (APP) may be neurotoxic and may impair synaptic plasticity and long-term memory in Alzheimer's disease, as suggested in murine models. To clarify these issues, we carried out a proteomic analysis of Chinese hamster ovary cells expressing APP CTFs and found that APP-CTF accumulation induced an increase in the level of phosphodiesterase 8B, suggesting that the hydrolysis of cyclic AMP was enhanced.