| 1. |
- Oberg, Johanna, et al.
(författare)
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Age related changes in brain metabolites observed by 1H MRS in APP/PS1 mice
- 2008
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 29:9, s. 1423-1433
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Tidskriftsartikel (refereegranskat)abstract
- Translational biomarkers in Alzheimer's disease based on non-invasive in vivo methods are highly warranted. (1)H magnetic resonance spectroscopy (MRS) is non-invasive and applicable in vivo in both humans and experimental animals. In vivo(1)H MRS and 3D MRI were performed on brains of double transgenic (tg) mice expressing a double mutant human beta-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 9.4T 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.
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| 2. |
- Westman, Eric
(författare)
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Magnetic resonance studies in Alzheimer's disease
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Alzheimer's disease (AD) is one of the most common forms of neurodegenerative disorders connected with gradual loss of cognitive functions such as episodic memory. The disease is related to pathological amyloid depositions and hyper phosphorilation of structural proteins in the brain which lead to progressive loss of function, metabolic alterations and structural changes in the brain. In vivo biomarkers need to be established to be able to set an early diagnosis, monitor disease progression and finally to observe pharmaceutical treatment effects. The aim of this thesis is to investigate the potential use of combining multivariate analysis with magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to monitor disease and treatment in AD. Due to the complexity of Alzheimer's disease, we hypothesized, that considering patterns of disease markers is more useful for the evaluation of patients or a study outcome, than making decisions based on single biomarkers alone. Studies I and II combine multivariate analysis with MRS to monitor disease and treatment effects in two different mouse models. Study III utilizes multivariate analysis in combination with different MRI measures (regional and global volumetric and cortical thickness measures) to discriminate between three groups, AD patients, MCI patients and healthy controls. Study IV investigates the added value of MRS in the early diagnosis of AD. In this study the multivariate models were built combining both MRI and MRS variables. The methods could successfully be applied in both animals and humans. Metabolic fingerprints of disease and treatment could be identified as well as patterns of atrophy. The combination of multivariate data analysis with different magnetic resonance measures is a powerful tool for identifying treatment effects and distinguishing between different subject groups. The multivariate combination of different measures was clearly more powerful and predictive than focusing only on single measures using traditional analysis.
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