Longitudinal investigation of neuroinflammation and metabolite profiles in the APPswe×PS1Δe9 transgenic mouse model of Alzheimers disease

摘要

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×PS1Δe9 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 [¹⁸F]DPA‐714 positron emission tomography and myo‐inositol levels using ¹H 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 [¹⁸F]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 style="fixed-case">NAA was observed in 18 m‐old style="fixed-case">TG mice when compared to style="fixed-case">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 style="fixed-case">TG animals, whereas style="fixed-case">NAA alterations occurring with age are exacerbated in the style="fixed-case">TG mice. These results support the role of neuroinflammation and metabolite alteration in style="fixed-case">AD and in ageing.