Biochemical and molecular studies of NMDA receptor subunits NR1/2A/2B in hippocampal subregions throughout progression of Alzheimer's disease pathology

• Published in: Neurobiology of disease Vol. 15; no. 1; pp. 80 - 92
• Main Authors: Mishizen-Eberz, Amanda J, Rissman, Robert A, Carter, Troy L, Ikonomovic, Milos D, Wolfe, Barry B, Armstrong, David M
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2004; Elsevier
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Disease Progression; Down-Regulation - genetics; Female; Hippocampus; Hippocampus - metabolism; Hippocampus - pathology; Hippocampus - physiopathology; Humans; Immunohistochemistry; In situ hybridization; Male; Middle Aged; Neurofibrillary Tangles - genetics; Neurofibrillary Tangles - metabolism; Neurofibrillary Tangles - pathology; Neurons - metabolism; Neurons - pathology; Neuropathology; NMDA receptor; Protein Subunits - genetics; Protein Subunits - metabolism; Receptors, N-Methyl-D-Aspartate - genetics; Receptors, N-Methyl-D-Aspartate - metabolism; RNA, Messenger - metabolism; Up-Regulation - genetics; Western blot; Western blot; NMDA receptor; In situ hybridization; Neuropathology; Alzheimer's disease; Hippocampus
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2003.09.016

Alzheimer's disease (AD) is characterized by loss of specific cell populations within selective subregions of the hippocampus. Excitotoxicity, mediated via ionotropic glutamate receptors, may play a crucial role in this selective neuronal vulnerability. We investigated whether alterations in NMDA receptor subunits occurred during AD progression. Employing biochemical and in situ hybridization techniques in subjects with a broad range of AD pathology, protein levels, and mRNA expression of NR1/2A/2B subunits were assayed. With increasing AD neuropathology, protein levels and mRNA expression for NR1/2B subunits were significantly reduced, while the NR2A subunit mRNA expression and protein levels were unchanged. Cellular analysis of neuronal mRNA expression revealed a significant increase in the NR2A subunit in subjects with moderate neurofibrillary tangle neuropathology. This investigation supports the hypothesis that alterations occur in the expression of specific NMDA receptor subunits with increasing AD pathologic severity, which is hypothesized to contribute to the vulnerability of these neurons.