Macroautophagy, which is a lysosomal pathway for the turnover of organelles and 
long-lived proteins, is a key determinant of cell survival and longevity. In 
this study, we show that neuronal macroautophagy is induced early in Alzheimer's 
disease (AD) and before beta-amyloid (Abeta) deposits extracellularly in the 
presenilin (PS) 1/Abeta precursor protein (APP) mouse model of beta-amyloidosis. 
Subsequently, autophagosomes and late autophagic vacuoles (AVs) accumulate 
markedly in dystrophic dendrites, implying an impaired maturation of AVs to 
lysosomes. Immunolabeling identifies AVs in the brain as a major reservoir of 
intracellular Abeta. Purified AVs contain APP and beta-cleaved APP and are 
highly enriched in PS1, nicastrin, and PS-dependent gamma-secretase activity. 
Inducing or inhibiting macroautophagy in neuronal and nonneuronal cells by 
modulating mammalian target of rapamycin kinase elicits parallel changes in AV 
proliferation and Abeta production. Our results, therefore, link 
beta-amyloidogenic and cell survival pathways through macroautophagy, which is 
activated and is abnormal in AD.