Amyloid pathology related alterations in the brain of transgenic mice models measured by diffusion kurtosis and magnetization transfer contrast magnetic

Date: 21 June 2017

Venue: UAntwerp, Campus Drie Eiken, Building Q, Promotiezaal - Universiteitsplein 1 - 2610 Wilrijk (Antwerp) (route: UAntwerpen, Campus Drie Eiken)

Time: 4:00 PM - 6:00 PM

PhD candidate: Christian Bigot

Principal investigator: Annemie Van der Linden, Marleen Verhoye

Short description: PhD defence Christian Bigot - Department of Biomedical Sciences


Alzheimer’s disease (AD) is a progressive neurodegenerative disease with a worldwide prevalence of about 35.6 million. By 2050, this number is expected to grow to 115.5 million. As such, AD carries an enormous burden on our economy and society. One of the major challenges today is to find an early biomarker for AD that can be used to demonstrate the start of the disease, as such an early biomarker, but also a biomarker to predict progression towards AD dementia and the effect of therapy on it. AD is characterized by amyloid pathology, tau pathology and neuronal loss. We have focused on amyloid pathology, generally accepted as one of the earliest events in the disease. We have used magnetic resonance imaging (MRI) because of its implicit soft tissue contrast, high spatial resolution and wide range of contrast offering enormous potential for the search for biomarkers for AD. We also used amyloidosis mice models since they enable to investigate the effect of amyloid pathology only. 

We have first used magnetization transfer contrast imaging (MTC-MRI) based on the hypothesis that amyloid pathology related brain alterations would modify the interaction between water and macromolecules. A proof of concept study in old APPPS1 and BRI mice yielded successful results. As such, a similar experiment was done on younger APPPS1 mice to evaluate the sensitivity and specificity of the method for earlier stages in the amyloid pathology. The results obtained from these studies also inspired us to use MTC-MRI to evaluate the therapeutic effect of functionalized liposomes. Following an equivalent hypothesis but here that amyloid related alterations would modify the diffusion properties of brain tissue water, we have extended diffusion weighted imaging to diffusion kurtosis imaging (DKI). DKI has a substantial higher sensitivity and more specific readout for grey matter distortions than conventional diffusion tensor MRI. A proof of concept study conducted in our lab showed the potential of the technique. Here, we have performed a longitudinal study to evaluate its potential as early marker for AD.

We demonstrated that both MTC-MRI and DKI have the potential for the detection and follow up of amyloid pathology induced brain alterations. MTC-MRI demonstrated also its potential to evaluate treatment targeting amyloid plaque removal. The results encourage further exploitation of these MRI techniques in preclinical AD where amyloid pathology remains the most prominent feature.