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Neuroscience Bulletin

, Volume 31, Issue 4, pp 491–504 | Cite as

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 ChuiEmail author
Original Article

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.

Keywords

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

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Copyright information

© Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • He-Cheng Wang
    • 1
  • Tao Zhang
    • 1
  • Bolati Kuerban
    • 1
  • Ying-Lan Jin
    • 1
  • Weidong Le
    • 2
  • Hideo Hara
    • 3
  • Dong-Sheng Fan
    • 4
  • Yan-Jiang Wang
    • 5
  • Takeshi Tabira
    • 6
  • De-Hua Chui
    • 1
    • 4
    Email author
  1. 1.Neuroscience Research Institute & Department of Neurobiology, School of Basic Medical SciencesPeking University Health Science CenterBeijingChina
  2. 2.Center for Translational Research of Neurology Disease, First Affiliated HospitalDalian Medical UniversityDalianChina
  3. 3.Division of Neurology, Department of Internal MedicineSaga University Faculty of MedicineSagaJapan
  4. 4.Department of NeurologyPeking University Third HospitalBeijingChina
  5. 5.Department of Neurology, Daping HospitalThird Military Medical UniversityChongqingChina
  6. 6.Department of Neurology, Graduate School of MedicineJuntendo UniversityTokyoJapan

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