@article{a5228cdb88894da68e1ad3c73d6d0e48,
title = " Longitudinal investigation of neuroinflammation and metabolite profiles in the APP swe ×PS1 Δe9 transgenic mouse model of Alzheimer's disease ",
abstract = " There is increasing evidence linking neuroinflammation to many neurological disorders including Alzheimer's disease (AD); however, its exact contribution to disease manifestation and/or progression is poorly understood. Therefore, there is a need to investigate neuroinflammation in both health and disease. Here, we investigate cognitive decline, neuroinflammatory and other pathophysiological changes in the APP swe ×PS1 Δe9 transgenic mouse model of AD. Transgenic (TG) mice were compared to C57BL/6 wild type (WT) mice at 6, 12 and 18 months of age. Neuroinflammation was investigated by [ 18 F]DPA-714 positron emission tomography and myo-inositol levels using 1 H magnetic resonance spectroscopy (MRS) in vivo. Neuronal and cellular dysfunction was investigated by looking at N-acetylaspartate (NAA), choline-containing compounds, taurine and glutamate also using MRS. Cognitive decline was first observed at 12 m of age in the TG mice as assessed by working memory tests. A significant increase in [ 18 F]DPA-714 uptake was seen in the hippocampus and cortex of 18 m-old TG mice when compared to age-matched WT mice and 6 m-old TG mice. No overall effect of gene was seen on metabolite levels; however, a significant reduction in NAA was observed in 18 m-old TG mice when compared to WT. In addition, age resulted in a decrease in glutamate and an increase in choline levels. Therefore, we can conclude that increased neuroinflammation and cognitive decline are observed in TG animals, whereas NAA alterations occurring with age are exacerbated in the TG mice. These results support the role of neuroinflammation and metabolite alteration in AD and in ageing. (Figure presented.).",
keywords = "Alzheimer's disease, animal model, magnetic resonance spectroscopy, neuroinflammation, positron emission tomography",
author = "Aisling Chaney and Martin Bauer and Daniela Bochicchio and Alison Smigova and Michael Kassiou and Davies, {Karen E.} and Williams, {Steve R.} and Herve Boutin",
note = "Funding Information: MK generously provided the precursor and cold reference for the production of [18F]DPA-714. HB was the grant holder of the European Union{\textquoteright}s Seventh Framework Programme (FP7/2007-2013) under grant agreement n°HEALTH-F2-2011-278850 (INMiND) which funded this work. The MR facility was supported through an equipment grant from BBSRC UK (BB/F011350). The developers of jMRUI (Stefan et al. 2009) and the support of it through the EU FP7 {\textquoteleft}TRANSACT{\textquoteright} (FP7-PEOPLE-2012-ITN-316679) are hereby acknowledged. The authors also thank all the personnel of the WMIC, especially Dr Michael Fairclough, Ms. Lidan Christie, Mr Michael Green, Mr Jamil Gregory, Ms Carol Brough and Ms Gemma Chapman for facilitating the study. We would also like to thank Drs Jack-Auty and Rebecca Montacute who helped with the breeding of some of the mice used in this study. All authors report no conflict of interest. Funding Information: MK generously provided the precursor and cold reference for the production of [18F]DPA-714. HB was the grant holder of the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement n?HEALTH-F2-2011-278850 (INMiND) which funded this work. The MR facility was supported through an equipment grant from BBSRC UK (BB/F011350). The developers of jMRUI (Stefan et?al.) and the support of it through the EU FP7 ?TRANSACT? (FP7-PEOPLE-2012-ITN- 316679) are hereby acknowledged. The authors also thank all the personnel of the WMIC, especially Dr Michael Fairclough, Ms. Lidan Christie, Mr Michael Green, Mr Jamil Gregory, Ms Carol Brough and Ms Gemma Chapman for facilitating the study. We would also like to thank Drs Jack-Auty and Rebecca Montacute who helped with the breeding of some of the mice used in this study. All authors report no conflict of interest. All experiments were conducted in compliance with the ARRIVE guidelines. Publisher Copyright: {\textcopyright} 2017 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry",
year = "2018",
month = feb,
doi = "10.1111/jnc.14251",
language = "English",
volume = "144",
pages = "318--335",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
number = "3",
}