Background.
Understanding the molecular dysfunction of neurodegenerative diseases such as Multiple Sclerosis (MS) or Alzheimers Disease (AD) is of great importance in order to develop new medicines or biomarkers. Disruption of the blood-brain barrier (BBB) and demyelination events plays a major role in disease activity in MS, as indicated by brain magnetic resonance imaging (MRI) contrast enhancement during relapses. Damage of the BBB may be initiated by systemic or CNS inflammation and contribute to escalation of pro-inflammatory responses within the CNS. In AD the behavioral symptoms correlate with the accumulation of plaques and tangles by highly insoluble protein aggregates of A-beta and Tau, respectively. The direct consequence is the damage and destruction of synapses that mediate memory and cognition.
Results & Conclusion
One study investigated the BBB breakdown and active inflammation in MS lesions by MRI followed by correlation analysis of new FLAIRs and Gd-enhancing lesions to plasma phenotype of EVs, plasma proteome and inflammation markers thus allowing description of the systemic inflammation. Several CD molecules and plasma markers could be correlated to the individual inflammatory profiles in the longitutinal study of 1.5 yr. Demyelination dynamics were studied in a cuprizone mouse model of MS by in-depth protein and PTM profiling and correlation to disease stages using microproteomics of brain regions. The study discovered multiple modifications linked to the stages of demyelination. Finally, we present the combination of microproteomics based investigation plaque in combination with AD optimized MALDI MS Imaging for detailed characterization of proteomic alterations in AD brain tissue compared to healthy individuals. By optimerization of the MALDI conditions the detection of proteoforms could be enhanced allowing an improved detection. Similar subregional fractionation of AD tissue allowed significantly improved detection of plaque content.
In summery, our studies have enabled novel insight into both AD and MS using proteomics tools.