Glutamatergic deficits are well-established neurochemical findings in Alzheimer’s disease (AD) and are thought to underlie both cognitive and behavioral symptoms of the disease. However, it is unclear whether subcortical ischemic vascular dementia (SIVD) and mixed SIVD/AD (MixD) manifest similar changes in the glutamatergic system. In this study, we measured the immunoreactivities of NMDA receptor GluN1, GluN2A, and GluN2B subunits in SIVD and MixD in postmortem neocortical tissues from a cohort of well-characterized, longitudinally followed-up patients with SIVD and MixD, together with age-matched controls. We found a significant reduction of GluN1 only in MixD, while significant increases of GluN2A and GluN2B were found only in SIVD. Furthermore, GluN1 loss and GluN2A/2B upregulation was associated respectively with higher Braak stages and lacunar infarct scores. Our data therefore suggest that the differential alterations of GluN subunits in SIVD and MixD may result from separate, interacting disease processes, and point to the potential utility of glutamatergic approaches for pharmacotherapy.

Reference

Mohamed NE, Lee JH, Francis PT, Esiri MM, Chen CP, Lai MK (This paper).