Trehalose Inhibits Aβ Generation and Plaque Formation in Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disease, and there has been no disease-modifying treatment for AD. Recent studies suggest that trehalose may have beneficial effect on neurodegenerative diseases through regulating autophagy and facilitating aggregated protein clearance. However, the effects of trehalose on AD-related neuropathologies are still unknown. Western blot was performed to examine the effects of trehalose on APP processing in vitro and in vivo. ELISA and immunohistochemical staining were conducted to measure Aβ production in vitro and neuritic plaque formation in APP23 transgenic mice, respectively. Trehalose treatment significantly decreased Aβ generation in HAW and 20E2 cells. Furthermore, trehalose treatment increased the levels of APP and its CTFs, and significantly reduced Aβ generation and neuritic plaque formation in APP23 mice. Our study showed that trehalose affected the APP processing both in vitro and in vivo and suggests that trehalose treatment may offer as a therapeutic strategy to ameliorate AD pathology by inhibiting Aβ generation and neuritic plaque formation.

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Abbreviations

AD:

Alzheimer’s disease

APP:

Amyloid β precursor proteins

Aβ:

Amyloid β protein

PS1:

Presenilin 1

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Availability of Data and Materials

The authors agree the availability upon request.

Funding

The study is supported by a UBC Centre for Brain Health Catalyst Grant/Donation from Ken & Sheila McArther to GYRH and WS. GYRH acknowledges support from the Ralph Fisher professorship from the Alzheimer Society of BC. WS was the holder of the Tier 1 Canada Research Chair in Alzheimer’s Disease. YL was the recipient of the China Scholarship Council’s graduate student award.

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Contributions

WS and GYRH conceived and designed the experiments; YL performed the experiments; YL and JW contributed reagents/materials/analysis tools; YL, JW, and WS wrote the paper. All authors reviewed the manuscript.

Corresponding authors

Correspondence to Ging-Yuek Robin Hsiung or Weihong Song.

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The authors declare that they have no conflict of interest.

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The animal experiments were approved by and conducted in accordance with the University of British Columbia Animal Care and Use Committee (Vancouver, BC, Canada) and the Canadian Institutes of Health Research (CIHR) guidelines.

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Liu, Y., Wang, J., Hsiung, G.R. et al. Trehalose Inhibits Aβ Generation and Plaque Formation in Alzheimer’s Disease. Mol Neurobiol 57, 3150–3157 (2020). https://doi.org/10.1007/s12035-020-01942-1

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Keywords

  • Alzheimer’s disease
  • Trehalose
  • APP
  • Neuritic plaque