Poster #034
In Vitro & In Silico Study of TREM2-Tau Interactions in Alzheimer’s Disease
Mentors: Win Ning Chen and Timothy Huang, PhD
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by neurofibrillary tau tangles, which lead to cognitive decline. Mutational variants of microglial receptor Triggering Receptor Expressed on Myeloid cells 2 (TREM2) are associated with increased AD risk. However, how TREM2 and its interactomes change with tau accumulation remains unclear. Here, we explore changes in TREM2 interactions with tau proteotoxicity. We compared TREM2 complexes bound to wildtype (WT) and PS19 mouse brain (expressing P301S tau associated with frontotemporal dementia), modeled TREM2-tau interactions, and predicted changes in TREM2 interactions over time. We identified that TREM2 binding factors, such as ACSL1 (a fatty acid acyl-CoA conjugation enzyme) and DAP12 (a TREM2 co-receptor), potentially interact with TREM2 at differing predicted rates with tau induction. This suggests that tau-dependent TREM2 interactions may modulate ACSL1 fatty acid metabolism or DAP12-mediated microglia activation. This may implicate novel TREM2-associated mechanisms associated with tau degeneration in AD and other tauopathies.