Thesis defense Nienke Timmer (Donders Series 45)
13 January 2011
Promotor: Prof.dr. H.P.H. Kremer, copromotors: Dr.ir. M.M. Verbeek, dr. R.M.W. de Waal
The interaction of heparan sulfate proteoglycans with the amyloid ß protein
Heparan sulfate proteoglycans are highly sulfated molecules containing a protein core with several sugar chains attached. In Alzheimer's disease, heparan sulfate proteoglycans can be found with the amyloid β deposits characteristic of Alzheimer's disease brains. In her thesis, Nienke Timmer describes that heparan sulfate proteoglycan production can be stimulated by amyloid β. In turn, amyloid β aggregation is stimulated by the heparan sulfate proteoglycans, with the sulfate groups of these proteoglycans being important mediators of this stimulation.
Furthermore, Nienke Timmer used a mouse model for Alzheimer's disease, that, like human patients, deposits amyloid β in its brain. Using this model, she now demonstrates that heparan sulfate proteoglycans do not accumulate with amyloid β in mouse brains to the same extent as they do in humans. Finally, she treated the mouse model with enoxaparin, an anticoagulant that is related to heparan sulfate proteoglycans. In these mice, enoxaparin improved memory, while also changing amyloid β levels. Enoxaparin may therefore be a new potential drug in the treatment of Alzheimer's disease.