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Reduced plaque size and inflammation in the APP23 mouse model for Alzheimer’s disease after chronic application of polymeric nanoparticles for CNS targeted zinc delivery

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posted on 2022-12-08, 15:57 authored by Antonietta Vilella, Daniela Belletti, Ann Katrin Sauer, Simone Hagmeyer, Tasnuva Sarowar, Martina Masoni, Natalia Stasiak, John MulvihillJohn Mulvihill, Barbara Ruozi, Flavio Forni, Maria Angela Vandelli, Giovanni Tosi, Michele Zoli, Andreas GrabruckerAndreas Grabrucker
A local dyshomeostasis of zinc ions in the vicinity of amyloid aggregates has been proposed in Alzheimer’s disease (AD) due to the sequestration of zinc in senile plaques. While an increase in zinc levels may promote the aggregation of amyloid beta (Aβ), increased brain zinc might also be beneficial rescuing some pathological alterations caused by local zinc deficiency. For example, increased Aβ degradation by metalloproteinases, and a reduction in inflammation can be hypothesized. In addition, zinc may allow a stabilization of the number of synapses in AD brains. Thus, to evaluate whether altering zinc-levels within the brain is a promising new target for the prevention and treatment of AD, we employed novel zinc loaded nanoparticles able to deliver zinc into the brain across the blood-brain barrier. We performed in vivo studies using wild type (WT) and APP23 mice to assess plaque load, inflammatory status and synapse loss. Furthermore, we performed behavioral analyses. After chronically injecting these nanoparticles for 14 days, our results show a significant reduction in plaque size and effects on the pro-inflammatory cytokines IL-6 and IL-18. On behavioral level we could not detect negative effects of increased brain zinc levels in APP23 mice and treatment with g7-NP-Zn normalized the observed hyperlocomotion of APP23 mice. Therefore, we conclude that a targeted increase in brain zinc levels may have beneficial effects in AD.

History

Publication

Journal of Trace Elements in Medicine and Biology;49, pp. 210-221

Publisher

Elsevier

Note

peer-reviewed

Other Funding information

Evangelisches Studienwerk Villigst e.V.

Rights

This is the author’s version of a work that was accepted for publication in Journal of Trace Elements in Medicine and Biology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Trace Elements in Medicine and Biology, 2017, 49, pp. 210-221 , https://doi.org/10.1016/j.jtemb.2017.12.006

Language

English

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  • Bernal Institute
  • Health Research Institute (HRI)

Department or School

  • Biological Sciences

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