Autophagy is involved in oral rAAV/Aβ vaccine-induced Aβ clearance in APP/PS1 transgenic mice

He Cheng Wang, Tao Zhang, Bolati Kuerban, Ying Lan Jin, Weidong Le, Hideo Hara, Dong Sheng Fan, Yan Jiang Wang, Takeshi Tabira, De Hua Chui

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)491-504
Number of pages14
JournalNeuroscience Bulletin
Volume31
Issue number4
DOIs
StatePublished - Aug 11 2015

Keywords

  • Akt/mTOR pathway
  • Alzheimer’s disease
  • Aβ clearance
  • autophagy
  • oral vaccination

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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