Regional changes in [3H]D-aspartate and [3H]TCP binding sites in Alzheimer's disease brains.
The specific binding of [3H]D-aspartate, a marker for the presynaptic glutamate uptake site, and [3H]N-(1-[2-Thienyl]cyclohexyl)-piperidine [( 3H]TCP), a high affinity ligand for the N-methyl-D-aspartate (NMDA)-associated phencyclidine binding site, was measured in homogenates of brain from normal subjects and from subjects with neuropathologically confirmed Alzheimer's disease. Alzheimer's disease was associated with a reduction in [3H]D-aspartate binding density in temporal cortex and caudate nucleus. By contrast, a reduction in the receptor density for [3H]TCP binding was only recorded in the frontal cortex. Thus, glutamate-containing nerve terminals are severely reduced in Alzheimer's disease, whilst the postsynaptic NMDA-phencyclidine receptor complex is much less affected. These findings have implications for theories of glutamate neurotoxicity in Alzheimer's disease.
Simpson
M D
MD
Department of Physiological Sciences, University of Manchester, U.K.
Royston
M C
MC
Deakin
J F
JF
Cross
A J
AJ
Mann
D M
DM
Slater
P
P
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D001224:Aspartic Acid / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000378:metabolism*
D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D001224:Aspartic Acid; C012058:tenocyclidine; D010622:Phencyclidine