Synaptic autophagy and the regulation of brain amyloid-β

Systemic attenuation of mTORC1 reduces brain Aβ levels, and potently activates autophagy in neurons. Aβ is generated at presynaptic terminals in association with neuronal activation, and it was recently shown that autophagosomes are abundant in presynaptic compartments.  How mTORC1 promotes Aβ production is not well understood.  We are using genetic tools to reduce mTORC1 exclusively in neurons of adult mice to test the hypothesis that neuronal mTORC1 promotes Aβ production by blocking autophagy at synaptic sites cell-autonomously.