Age related changes in brain metabolites observed by 1H MRS in APP/PS1 mice
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- 作者：Johanna Oberg ; Christian Spenger ; Fu-Hua Wang ; Anders Andersson ; Eric Westman ; Peter Skoglund ; Dan Sunnemark ; Ulf Norinder ; Tomas Klason ; Lars-Olof Wahlund ; Mattias Lindberg
- 关键词：APP/PS1 ; Amyloid ; Presenilin ; Magnetic resonance spectroscopy (MRS) ; Spectroscopy ; Multivariate data analysis ; PLS-DA ; Alzheimer's disease
- 刊名：Neurobiology of Aging
- 出版年：2008
- 出版时间：September 2008
- 年：2008
- 卷：29
- 期：9
- 页码：1423-1433
- 全文大小：962 K
文摘
Translational biomarkers in Alzheimer's disease based on non-invasive in vivo methods are highly warranted. 1H magnetic resonance spectroscopy (MRS) is non-invasive and applicable in vivo in both humans and experimental animals. In vivo 1H MRS and 3D MRI were performed on brains of double transgenic (tg) mice expressing a double mutant human β-amyloid precursor protein APP(K670N,M671L) and human mutated presenilin gene PS1M146L, and wild-type (wt) littermates at 2.5, 6.5 and 9 months of age using a 9.4 T magnet. For quantification, LCModel™ was used, and the data were analyzed using multivariate data analysis (MVDA). MVDA evidenced a significant separation, which became more pronounced with age, between tg and wt mice at all time points. While myo-inositol and guanidoacetate were important for group separation in young mice, N-acetylaspartate, glutamate and macrolipids were important for separation of aged tg and wt mice. Volume segmentation revealed that brain and hippocampus were readily smaller in tg as compared to wt mice at the age of 2.5 months. Amyloid plaques were seen in 6.5 and 9 months, but not in 2.5 months old animals.
In conclusion, differences in brain metabolites could be accurately depicted in tg and wt mice in vivo by combining MRS with MVDA. First differences in metabolite content were readily seen at 2.5 months, when volume defects in tg mice were present, but no amyloid plaques.