title: Differential alterations of cortical glutamatergic binding sites in senile dementia of the Alzheimer type.
abstract: Involvement of cortical glutamatergic mechanisms in senile dementia of the Alzheimer type (SDAT) has been investigated with quantitative ligand-binding autoradiography. The distribution and density of Na(+)-dependent glutamate uptake sites and glutamate receptor subtypes--kainate, quisqualate, and N-methyl-D-aspartate--were measured in adjacent sections of frontal cortex obtained postmortem from six patients with SDAT and six age-matched controls. The number of senile plaques was determined in the same brain region. Binding of D-[3H]aspartate to Na(+)-dependent uptake sites was reduced by approximately 40% throughout SDAT frontal cortex relative to controls, indicating a general loss of glutamatergic presynaptic terminals. [3H]Kainate receptor binding was significantly increased by approximately 70% in deep layers of SDAT frontal cortex compared with controls, whereas this binding was unaltered in superficial laminae. There was a positive correlation (r = 0.914) between kainate binding and senile plaque number in deep cortical layers. Quisqualate receptors, as assessed by 2-amino-3-hydroxy-5-[3H]methylisoxazole-4-propionic acid binding, were unaltered in SDAT frontal cortex compared with controls. There was a small reduction (25%) in N-methyl-D-aspartate-sensitive [3H]glutamate binding only in superficial cortical layers of SDAT brains relative to control subjects. [3H]Glutamate binding in SDAT subjects was unrelated to senile plaque number in superficial cortical layers (r = 0.104). These results indicate that in the presence of cortical glutamatergic terminal loss in SDAT plastic alterations occur in some glutamate receptor subtypes but not in others.
authors.affiliation: Wellcome Surgical Institute, University of Glasgow, Scotland, United Kingdom.
authors.forename: D T
authors.initials: DT
authors.lastname: Chalmers
authors.forename: D
authors.initials: D
authors.lastname: Dewar
authors.forename: D I
authors.initials: DI
authors.lastname: Graham
authors.forename: D N
authors.initials: DN
authors.lastname: Brooks
authors.forename: J
authors.initials: J
authors.lastname: McCulloch
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D001224:Aspartic Acid / Q000378:metabolism; D001345:Autoradiography; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005971:Glutamates / Q000378:metabolism*; D006801:Humans; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D007608:Kainic Acid / Q000378:metabolism; D008297:Male; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D012016:Reference Values; D014316:Tritium; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
chemical_list: D005971:Glutamates; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D014316:Tritium; D007051:Ibotenic Acid; D001224:Aspartic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid