Shining light on Alzheimer pathology: Photoswitchable fluorescent molecular probes for advanced imaging of amyloid-beta polymorphism

The aim of this project is to develop novel advanced photoresponsive fluorescent probes based on hydrazone derivatives.The purpose is to probe amyloid-β (Aβ) proteine aggregates which are a main pathology of Alzheimer disease, to achieve a deeper understanding of plaques polymorphism.

Design of new hydrazone derivatives will build upon previous successful molecular designs but with incorporation of the photoswitchable part, which allow for photoinduced fluorescence modulation, and introduce a new probing tool.The first 2-years the project will be carried out in the group of Prof Aprahamian, at Dartmouth (USA).

Design, synthesis and tests in solution will be done to identify the best hydrazones for probing Aβ polymorphism.

The obtained probes will then be used in the 3rd year to interrogate Aβ pathology in mouse models and human brains, using confocal and hyperspectral imaging in the group of Assoc Prof Hanrieder at Gothenburg University.

Fluorescent imaging will be correlated to immunohistochemistry and MALDI imaging specific chemical information, to achieve a deeper understanding of plaques morphotypes.Development of new advanced fluorescent probes will have the impact of expanding the available bioimaging tools to image Aβ and other pathologies.

Knowledge of what subcellular mechanisms and structures are involved in Aβ-mediated pathogenesis will open the way for developing novel biomarkers and tailored strategies to mitigate these processes.