Decoding Alzheimer’s Disease at the Molecular Level: Computational Modeling of Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) Inhibition using DNA-Based Aptamers

Alzheimer’s Disease is a progressive brain disorder that causes memory loss, confusion, and difficulty with thinking and daily activities.TREM2 is a protein that is found on the surface of microglial cells in the brain that helps regulate the immune response and clear damaged cells.An aptamer is a short strand of DNA or RNA that folds into a specific shape, allowing it to bind tightly and specifically to a target molecule, such as a protein or drug. Our aim is to computationally model and analyze the binding interactions between the TREM2 protein and S6 peptides/aptamers for the early detection of Alzheimer’s disease. We hypothesize that specific S6 peptides and designed aptamers can bind strongly to the extracellular domain of TREM2, enabling sensitive detection of Alzheimer’s disease biomarkers. We have performed computational modeling of the TREM2 protein using aptamers and identified an aptamer that binds strongly and blocks the protein. These computational results show that the aptamer S62 binds strongly to the TREM2 protein and could be a good candidate for TREM2 protein inhibition. This work will help in developing targeted methods to treat diseases like Alzheimer’s, where aptamers can be de- signed to bind harmful proteins and help remove or block them.