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STUDIES ON THE USE OF MRI TO DETECT β-AMYLOID LOAD IN THE BRAINS OF 5XFAD ALZHEIMER’S MODEL MICE

      Background

      A rapid method capable of detecting early signs of Alzheimer’s Disease would revolutionise diagnosis, treatment and outcome of this neurodegenerative disease.

      Methods

      We have used the 5XFAD mice model of Alzheimer;s Disease developed by Oakley et al (2006) to see if MRI can be used to detect changes. 5XFAD and wild-type mice were imaged in a 4.7 T Varian horizontal-bore MRI system to generate T1 quantitative maps using the spin-echo multi-splice sequence.

      Results

      Scanning was followed by immunostaining for GFAP, Iba-1 and beta-amyloid, which showed that amyloidosis developed at 2.5 months in the FAD mouse, and gliosis at 5 months, but not in the wt mice. However, MRI T1 relaxation times were not significantly different to those of age-matched wt mice, indicating that MRI T1 alone would not be a sensitive method of detecting disease initiation or progression (Spencer et al., 2016). In attempts to enhance the MRI response in T1 or T2 node, we synthesised Gd-complexed beta-amyloid-binding contrast agents, comprising peptides from the b-amyloid sequence that were found to have high self-aggregating affinity for b-amyloid itself, covalently linked to DOTA, complexed to an atom of 157 gadolinium; biodistribution of 153-Gd labelled analogue of the contrast agent was found to preferentially distribute to liver in mice, with very little adsorbed into brain, so focussed ultrasound and reagent co-injection with microbubbles was used to gain an enhance MRI T1 profiile in the 5XFAD mice compared to WT mice (Matharu et al. 2015)

      Conclusions

      MRI T1 was not sufficient to detect amyloidosis or gliosis in 5XFAD Alzheimer mice models. Uptake of a contrast agent could be a useful method to gain visualisation of beta-amyloid deposits at early stages of Alzheiemer's Matharu B, Spencer N, Howe F, and Austen B (2015) Gadolinium-complexed Ab-binding contrast agents for MRI diagnosis of Alzheimer’s Disease. Neuropeptides 53 http://dx.doi.org/10.1016/j.npep.2015.07.001 Oakley H, et al (2006) J Neurosci 26)40); 10129-10140 Spencer NG, Lovell DP, Elderfield K, Austen B and Howe FA. (2016) Can MRI T1 be used to detect early changes in 5XFAD Alzheimer’s mouse brain. Magn Reson. Mater.Phy http://dx.doi.org/1007/s10334-016-0593-9.