Consortium Aggregation and Degeneration

Alzheimer’s disease and frontotemporal dementia (FTD) are the two most common degenerative dementias. No treatment is available for either entity that stops the progression of the disease. Both these types of dementia are characterized by the build up of protein deposits.

In Alzheimer’s disease two main proteins form polymers. The extracellular amyloid plaques consist largely of polymerized amyloid ß-peptides, whereas the intracellular neurofibrillary tangles are made up of the microtubule-associated protein Tau. TDP-43 is the major protein found in inclusions of frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD U).

The consortium for “Aggregation and Degeneration” comprises four research alliances (RA I to RA IV). Within each research alliance several internationally recognized scientists, with the help of five core units (C 1 to C5), research:

• the disease pathogenesis of both disorders,
• work out similarities and differences between them,
• and thereby aim to identify new treatment targets.

Specifically we will study factors that initiate, facilitate and modulate protein aggregation and the generation of the peptides from their precursors that are found to be aggregated.

To achieve these aims, and also to validate these treatment targets and potential therapeutic compounds for their use in patients, we will use different model systems including primary cell cultures, zebrafish, the fruit fly (drosophila) and transgenic mice. Genetic and pharmacological screens will also be carried out on these models in order to identify new treatment targets and then these candidates tested and validated.

To translate these studies into clinical trials in patients we will also establish biomarkers that will make it possible to follow the efficacy of such dugs over time on protein aggregation and inflammatory processes. Examples of techniques to track such biomarkers are PET and multiphoton in vivo imaging.