Peter Sjövall
SP Technical Research Institute of Sweden
Sweden
Studies of molecular mechanisms in Alzheimer's disease using imaging mass spectrometry
Swedish Research Council
652,883
01/01/2016
4
Alzheimer's disease & other dementias
Despite considerable research efforts, no effective drugs able to cure or even slow down the progress of Alzheimers disease (AD) are yet in sight. An important part of the problem is that AD is an exceedingly complex disease with numerous biomolecular processes occurring in parallel at many different locations in the brain. The purpose of this project is to mobilize novel and advanced molecular imaging technologies and to use these to study critical and yet unresolved issues regarding protein aggregation in AD, including the role of lipids, ApoE and so called chaperones in the aggregation of amyloid-beta peptides (Abeta), eventually leading to the formation of senile plaques. New information on these issues will be obtained by simultaneous imaging of a large number of proteins and lipids in and around Abeta plaques in AD transgenic mouse brains and in human AD brain tissue. A new analytical approach will be used, combining several state-of-the-art molecular imaging methods, including fluorescence microscopy, imaging MALDI and a recently developed method based on time-of-flight secondary ion mass spectrometry (TOF-SIMS), capable of parallel imaging of multiple proteins and lipids in tissue sections at subcellular (down to submicron) resolutions. The results are expected to provide new knowledge that may significantly improve the understanding of the molecular processes responsible for the disease and thereby contribute to the development of effective drugs against AD.