Enhancement of the nonamyloidogenic pathway by exogenous NGF in an Alzheimer transgenic mouse model

Nerve growth factor (NGF) is an important nerve cell growth regulatory factor and has an indispensable role in the development, survival and regeneration of the cholinergic basal forebrain (CBF) neurons, and it has multiple targets when used for Alzheimer’s Disease (AD) therapy. In this study, we observed whether NGF can affect cholinergic neurons to change amyloid-β precursor protein (APP) metabolism process and reduce amyloidosis in AD brains. NGF was administered intranasally to APP/PS1 double-transgenic mice for 14 weeks. We observed an increase in APP695 and ADAM10 and a decrease in BACE1 and PS1 protein levels and, subsequently, a reduction in Aβ1–40 and Aβ1–42 levels and Aβ burden were present in NGF-treated mice brains, suggesting that NGF enhanced the APP nonamyloidogenic cleavage pathway and reduced the Aβ generation in the APP/PS1 transgenic mice brains.