The imbalance between ß-amyloid (Aß) generation and clearance plays a fundamental role in the pathogenesis of Alzheimer's disease (AD). The sporadic form of AD is characterized by an overall impairment in Aß clearance. Immunotherapy targeting Aß clearance is believed to be a promising approach and is under active clinical investigation. Autophagy is a conserved pathway for degrading abnormal protein aggregates and is crucial for Aß clearance. We previously reported that oral vaccination with a recombinant AAV/Aß vaccine increased the clearance of Aß from the brain and improved cognitive ability in AD animal models, while the underlying mechanisms were not well understood. In this study, we first demonstrated that oral vaccination with rAAV/Aß decreased the p62 level and up-regulated the LC3B-II/LC3B-I ratio in APP/PS1 mouse brain, suggesting enhanced autophagy. Further, inhibition of the Akt/mTOR pathway may account for autophagy enhancement. We also found increased anti-Aß antibodies in the sera of APP/PS1 mice with oral vaccination, accompanied by elevation of complement factors C1q and C3 levels in the brain. Our results indicate that autophagy is closely involved in oral vaccination-induced Aß clearance, and modulating the autophagy pathway may be an important strategy for AD prevention and intervention.

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The temperature behavior of multiple tunnel junction (MTJ) devices made with sub-5-nm gold islands is investigated. A smooth decrease of the Coulomb gap with increasing temperatures is observed. The critical temperature beyond which the Coulomb blockade effect is suppressed is found to change as a function both of the average size of the islands and of the size of the two-dimensional (2D) array of islands forming the MTJ. This latter property is attributed to the role of disorder in the 2D array. Results are compared with Monte Carlo simulations of current transport through highly disordered 2D arrays which reproduce the experimental evolution of the Coulomb gap with temperature.