Toma de Posesión como Académico Extranjero del Prof. Dr. Frits Kamp

Alzheimer disease (AD) is the most common neurodegenerative disease worldwide. It is widely believed that the disease is caused by plaque formation of amyloid β-peptide (Aβ) in the brain of affected patients. Aβ peptides are generated by processing of the amyloid precursor protein (APP), a type I membrane protein. Two membrane-bound proteases are involved in this process: β- and γ-secretase, resulting in release of Aβ peptides into the extracellular space. Being obvious AD drug targets, potent Aβ-lowering inhibitors have been developed for both β- and γ-secretase. However, these drugs have unfortunately failed in clinical trials due to severe side effects. However, recent vaccination Aβ therapies are promising.
The causes for the Aβ imbalances in common sporadic forms of AD are not clear. One possibility is that membrane lipid changes that occur with aging causally contribute to onset of the disease. In our laboratory, by investigating various lipid classes, we found that its surrounding lipids potently modulate the activity of γ-secretase. In particular, we worked out in detail that membrane thickness has a substantial influence on the activity and precision of γ-secretase in the generation of Aβ. More recently, by focusing on neurosteroids, we found that the latter also have a major impact. The studies might open new venues in the understanding of the causes and treatment of AD.