Alzheimer mutations stabilize synaptotoxic γ-secretase-substrate complexes
Sujan Devkota, Rui Zhou, Vaishnavi Nagarajan, Masato Maesako, Hung Nguyen Do, Arshad Ali Noorani, Caitlin Overmeyer, Sanjay Bhattarai, Justin T. Douglas, Anita Saraf, Yinglong Miao, Brian D. Ackley, Yigong Shi, Michael S. Wolfe
This study shows that Alzheimer's mutations stabilize harmful enzyme-substrate complexes in gamma-secretase, leading to synaptic loss rather than the released Aβ peptides being the primary cause.
bioRxiv · Sep 8, 2023 · PreprintNeuroscience