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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
Vilella, Antonietta; Belletti, Daniela; Sauer, Ann Katrin; Hagmeyer, Simone; Sarowar, Tasnuva; Masoni, Martina; Stasiak, Natalia; Mulvihill, John J.E; Ruozi, Barbara; Forni, Flavio; Vandelli, Maria Angela; Tosi, Giovanni; Zoli, Michele; Grabrucker, Andreas M.
The full text of this article will not be available in ULIR until the embargo expires on the 27/12/2017 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. ACCEPTED peer-reviewed
Keyword(s): blood brain barrier; Alzheimer; drug delivery; nanoparticle; amyloid
Publication Date:
2017
Type: Journal article
Peer-Reviewed: Yes
Language(s): English
Institution: University of Limerick
Citation(s): COST
Journal of Trace Elements in Medicine and Biology;49, pp. 210-221
http://www.sciencedirect.com/science/article/pii/S0946672X17308428
https://doi.org/10.1016/j.jtemb.2017.12.006
PRIN 2010-2011 - protocollo: 2010H834LS_003
Publisher(s): Elsevier
First Indexed: 2018-07-11 06:25:52 Last Updated: 2018-07-11 06:25:52