Project number 29

Cellular and network dysfunctions in the early stages of Alzheimer’s Disease 

Alzheimer´s Disease (AD) alters cognition and induces memory loss, language problems and failure to recognize objects and people. The major challenge for AD research is to understand the complex cellular reactions in the prolonged pre-clinical development of the disease, which may be the best available time window for therapeutic intervention. Early stages of AD are characterized by the seeding, aggregation, and prion-like spreading of abnormally folded amyloid Aβ peptide and Tau in the brain of patients, which leads to the appearance of amyloid plaques and neurofibrillary tangles. However, it is poorly understood how amyloid Aβ and Tau pathologies interact and contribute to the slow deterioration of cell and network function, and eventually behavior. 
Research Goals: The goal of the project is to identify and follow the early effects of amyloid Aβ stress and to map the further spread of pathophysiological changes at the level of single cells and network function in the hippocampal-entorhinal episodic memory system. Initially, the focus will be on amyloid Aβ induced pathology in a humanized APP knock-in mouse model. This will be followed by testing how Tau modulates and exacerbates the amyloid Aβ effects, as the two pathologies meet in the hippocampus.  
Relevant expertise of research groups: The project will combine complementary methods (cell biology, transcriptomics, neurophysiology in behaving animals) to address the question from different angles and at multiple levels (cells, network and behavior). Candidates will spend roughly equals amount of time in both labs.

Keywords
Alzheimer’s Disease, hippocampus, memory, cell biology, neurophysiology

Supervisors
Fabian Kloosterman, Neuro-Electronics Research Flanders, Imec, Leuven
Bart De Strooper, VIB Center for the Biology of Disease, KU Leuven, Leuven