ZonMW Dementia Fellowship for Kim de Kleijn
Kim de Kleijn (The Candidate Center/AUMC/FGA) received the ZonMW Dementia Fellowship (3 years) to set-up an independent research line to study the TREM receptor family and its relevance for microglia functioning in context of Alzheimer’s disease.
Microglia express a number of activating receptors that tightly control their phenotype and function. While the mechanism of TREM2-receptor activation and signaling in microglia activation in AD is known, the function of the other TREM-receptors in microglia is not clear. Yet, these receptors are relevant to AD, as an AD protective genetic variant has been found in TREML2, and the expression of the secreted extracellular portion of TREM1 in CSF correlates strongly with AD disease progression.
What kind of interactions the TREM receptor family engages in is unclear, because their ligands and hence extracellular triggers for activation are unknown. Kim will identify receptor-ligand pairs for all TREM receptors using genome-wide CRISPR screening and proteomics approaches, and hereby find new tools to fine-tune the activation of microglia via modulation of the TREM-receptor family.
Impaired functioning of microglia cells has been strongly associated with brain pathology in AD. The knowledge generated by this project on TREM-receptor signaling in the fine-tuning of microglia activation gives insight into AD disease aetiology and contributes to the possible development of new AD-therapeutics.