University of Gothenburg
Translational studies on APP and β-amyloid for Alzheimer's disease pathogenesis
Swedish Research Council
Alzheimer's disease & other dementias
Recent research advances on Alzheimer’s disease (AD) have been translated into new disease-modifying amyloid β (Aβ) drug candidates, but these have shown disappointing clinical effects. This may be due to that amyloid precursor protein (APP) processing and Aβ metabolism is much more complicated than previously believed, with a large number of processing pathways, which may have significance both for disease pathogenesis and development of therapies. We will use novel techniques to perform true translational studies, where the same processing pathways are studied in preclinical cell- and animal experiments, as well as in clinical neurochemical studies and clinical trials. The specific aims are to: 1) develop novel selected reaction monitoring (SRM)-based techniques for APP isoforms and β-amyloid (Aβ) species; 2) use these techniques to study APP and Aβ in cell culture and animal models with the aim to identify the enzymes regulating their metabolism, and as reference methods for use both as diagnostic and theragnostic markers; 3) develop analytical methods for Aβ oligomers, γ-secretase processing (Notch-β) and synaptic degeneration, to evaluate the role of these processes in AD pathogenesis, and as diagnostic and theragnostic markers. The aims are to get valid data on the molecular pathogenesis of AD, develop novel diagnostic tools (biomarkers) and theragnostic markers to monitor treatment effects.