Overall objectives of the research program
The onset of Alzheimer's Disease (AD) can only be directly attributed to genetic predisposition or genetic factors in approximately 10% of cases. The assumption is therefore that the large majority of cases (sporadic AD) is caused by harmful environmental factors. However, very little is known about this. More insight into the molecular mechanisms by which such environmental factors cause AD will enable better and earlier diagnostics, more effective pharmacotherapy and optimized preventive strategies. This offers great opportunities for innovation and valorisation.
BReIN's research program therefore aims at a better understanding of the role of harmful environmental factors in the development and progression of AD. It will also be investigated whether there is a greater sensitivity to these adverse environmental factors in certain AD patients.
In order to unravel these molecular mechanisms, given the complexity of the neuronal systems involved, with sufficient depth, BReIN uses very powerful 'omics technologies with a high resolution in analyzing molecular processes. This concerns in particular 'next generation sequencing' (NGS), supplemented with 'imaging' data (CT, MRI, PET). The DNA / RNA analyzes will be performed - post mortem in brain tissue, as well as at different stages of the course of the disease in blood and cerebrospinal fluid (CSF) - in patients with sporadic AD. NGS analyzes will also be used in experimental in vitro research in which pluripotent stem cell models (iPSC) will investigate the role of chemical environmental factors in particular. The iPSCs will be cultured in such a way that they differentiate into the appropriate phenotype for AD. Results of this mechanistic in vitro study in iPSC AD models will be linked translationally with data from sporadic AD patients.
BReIN will therefore generate very large quantities of molecular data that will also be supplemented with MRI scans from AD patients. This requires that a tailored data infrastructure is created within which data are stored reliably, standardized and sustainably and which enables conducting the more complex statistical and mathematical analyses that are relevant for disclosing molecular mechanisms induced by chemical environmental factors.
The central objective of the BReIN research is therefore to perform translational mechanistic research on the involvement of adverse environmental factors in the development of sporadic AD and to create a new e-Infrastructure for the collection, storage and integrative analysis of multiple complex data types thus enabling to design strategies for diagnosis, therapy and prevention.