Affiliations: [a] Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore | [b] Wolfson Centre for Age-Related Diseases, King's College London, London, UK | [c] Oxford Project to Investigate Memory and Aging (OPTIMA), University of Oxford, John Radcliffe Hospital, Oxford, UK | [d] Memory, Aging and Cognition Centre, National University Health System, Singapore, Singapore
Correspondence:
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Correspondence to: Mitchell K.P. Lai, PhD, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Level 5, CRC Building (MD11), 10 Medical Drive, Singapore 117597, Singapore. Tel.: +65 6601 2678; Fax: +65 6873 7690; E-mail: mitchell.lai@dementia-research.org.
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.
