The role of ApoE-mediated neuroinflammation in the progression along the pathogenetic axis in AD. (R-10980)

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder imposing an unbearable socio-economic burden worldwide. Current therapeutic approaches fail to halt AD progression, indicating the need for new strategies and more complete AD models, the focus of this project. To provide clinical translational value, models which recapitulate the full Amyloid-Tau-Neurodegeneration (A/T/N) axis of AD are imperative and developed here. Furthermore, a protective APOE mutation was identified ADAD carriers, delaying onset of Tau pathology along with clinical symptoms. Furthermore, ApoE4 has been identified as first genetic risk factor for AD, while ApoE2 seems to confer protection. Here, we investigate how ApoE and ApoE variants modulate inflammation thereby affecting amyloid-induced Tau pathology and subsequent Tau-induced neurodegeneration. First, the microglial profiles will be identified at different AD stages, using our own developed, robust A/T/N model. Second, we will interfere in the microglial response to the neurodegenerative processes to reveal the microglial impact in progression along the A/T/N axis. Third, the role of ApoE and interaction partners in A/T/N progression will be studied.

Keywords:Neuroinflammation, Neurology

Disciplines:Inflammation, Neuroanatomy, Neurological and neuromuscular diseases