title: Differential alterations of neocortical GluN receptor subunits in patients with mixed subcortical ischemic vascular dementia and Alzheimer's disease.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  To measure the immunoreactivities of NMDA receptor GluN1, GluN2A, and GluN2B subunits in SIVD and MixD.
  
  
  METHODS
  Postmortem neocortical tissues from a cohort of well-characterized, longitudinally followed-up patients with SIVD and MixD, together with age-matched controls, were processed for immunoblotting with GluN subunit-specific antibodies.
  
  
  RESULTS
  There was 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.
  
  
  CONCLUSIONS
  Our data 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.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Nur-Ezan
authors.initials: NE
authors.lastname: Mohamed
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Jasinda H
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London, UK.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Francis
authors.affiliation: Oxford Project to Investigate Memory and Aging (OPTIMA), University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Esiri
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore Memory, Aging and Cognition Centre, National University Health System, Singapore, Singapore.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore Wolfson Centre for Age-Related Diseases, King's College London, London, UK Memory, Aging and Cognition Centre, National University Health System, Singapore, Singapore.
authors.forename: Mitchell K P
authors.initials: MK
authors.lastname: Lai
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D015140:Dementia, Vascular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015151:Immunoblotting; D008137:Longitudinal Studies; D008297:Male; D019579:Neocortex / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012720:Severity of Illness Index
chemical_list: D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C485668:GRIN1 protein, human; C121001:NR2B NMDA receptor
keywords: Alzheimer's disease; GluN receptors; mixed dementia; neurochemistry; subcortical ischemic vascular dementia