Longitudinal investigation of neuroinflammation and metabolite profiles in the APP swe ×PS1 Δe9 transgenic mouse model of Alzheimer's disease

Aisling Chaney, Martin Bauer, Daniela Bochicchio, Alison Smigova, Michael Kassiou, Karen E. Davies, Steve R. Williams, Herve Boutin

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

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.).

Original languageEnglish
Pages (from-to)318-335
Number of pages18
JournalJournal of Neurochemistry
Volume144
Issue number3
DOIs
StatePublished - Feb 2018

Keywords

  • Alzheimer's disease
  • animal model
  • magnetic resonance spectroscopy
  • neuroinflammation
  • positron emission tomography

Fingerprint

Dive into the research topics of 'Longitudinal investigation of neuroinflammation and metabolite profiles in the APP swe ×PS1 Δe9 transgenic mouse model of Alzheimer's disease'. Together they form a unique fingerprint.

Cite this