BDNF and Alzheimer disease: Given that BDNF binding to NTRK2 activates key intracellular signaling pathways, including PI3K–AKT and MAPK–ERK, which are essential for neuronal survival and resilience to cellular stress (103), the reduced interaction of this LR pair likely reflects a loss of inter-subregion neurotrophic support, driven by increasing pathological burden in AD.