2026-04-17T03:13:31Zhttps://recercat.cat/oai/request

oai:recercat.cat:2072/4835912025-05-08T16:23:21Zcom_2072_98col_2072_378192

00925njm 22002777a 4500 dc Escamilla, Sergio author Badillos Rodríguez, Raquel author Comella i Carnicé, Joan Xavier author Solé Piñol, Montserrat author Pérez-Otaño, Isabel author Mut, Jose V. Sánchez author Sáez-Valero, Javier author Cuchillo-Ibáñez, Inmaculada author 2024 Synaptic and extrasynaptic distribution of N-methyl-D-aspartate receptors (NMDARs) has not been addressed in the brain from Alzheimer's disease (AD) subjects, despite their contribution to neurodegeneration. We have developed a protocol to isolate synaptic and extrasynaptic membranes from controls and AD frontal cortex. We characterized the distribution of the NMDAR subunits GluN2B, GluN2A, GluN1, and GluN3A, as well as post-translational modifications, such as phosphorylation and glycosylation. Lower levels of synaptic GluN2B and GluN2A were found in AD fractions, while extrasynaptic GluN2B and GluN1 levels were significantly higher; GluN3A distribution remained unaffected in AD. We also identified different glycoforms of GluN2B and GluN2A in extrasynaptic membranes. Synaptic Tyr1472 GluN2B phosphorylation was significantly lower in AD fractions. Reduction of synaptic NMDAR subunits, particularly for GluN2B, is likely to contribute to synaptic transmission failure in AD. Additionally, the increment of extrasynaptic NMDAR subunits could favor the activation of excitotoxicity in AD. http://hdl.handle.net/2072/483591 Alzheimer's disease Extrasynaptic GluN1 GluN2A GluN2B GluN3A Human NMDA Tyr1336 Tyr1472 Synaptic and extrasynaptic distribution of NMDA receptors in the cortex of Alzheimer's disease patients