The study investigates the relationship between impaired MHC2M complex and Alzheimer's disease, AD, in vitro and human AD samples, finding that eoligomers disassemble the MHC2M complex, leading to reduced interactions with neural cell adhesion molecule 1, NCAM1, a novel interactor of neuronal MHCI, and decreased signalling. The study suggests modulation of MHCI stability may be a potential therapeutic target for restoring synaptic function in AD.