Alzheimer’s disorder (AD) is characterized by depositions of toxic aggregates of amyloid beta (called senile plaques) and enhance phosphorylation of tau (forming so-called tangles) with neurodegeneration as a downstream event. Another common feature of AD is vasculopathy, seen for example as increased blood brain barrier (BBB) permeability and loss of pericytes. Since pericytes is crucial for BBB stability and removal of amyloid beta from the brain, it has been hypnotized that the AD related pericyte loss in part underly the brain accumulation of amyloid beta seen in AD patients. Hence pericyte loss could be an early key event in the pathogenesis of AD. The underlying cause to the pericyte death is however yet not known.
We have recently discovered that a peptide secreted form the pancreas has a tremendous toxic impact on brain pericytes. This peptide, called IAPP, is foremost linked to type 2 diabetes pathology as it is known to form cell toxic plaques in peripheral organs (pancreas, hart, kidney and so on) of these patients. Plaques of IAPP has however also lately been found in the T2D and AD brain and some studies suggest that IAPP can trigger the formation of amyloid beta plaques. In view of the potential implication of IAPP in AD and due to strong toxic impact of IAPP on brain pericytes, we hypothesis that IAPP-induced pericyte death underly the pericyte loss in AD patients- leading to the reduced clearance of amyloid beta and neurodegeneration seen in AD. To explore this hypothesis, we plan to investigate how IAPP affects pericytic function (amyloid beta clearance and glycogenolysis) by the use of experimental studies on cultured pericytes. Results will be verified in postmortem brain tissue. The planned project, which is suitable for a Master student, will thus include cell culture studies as well as postmortem studies and analysis will be performed by different protein assays, immunostainings and PCR. The candidate should have basic knowledge of biochemistry and have some experience in cell culture studies. The project will be conducted at Wallenberg lab, Malmö.
Clinical Memory Research Unit
Dept of Clinical Sciences, Malmö
The Wallenberg Lab, 2nd floor
Inga Marie Nilssons Gata, entrance 53
Skåne University Hospital Malmö
Malin Wennström email@example.com