Glutamate receptor dysregulation in the hippocampus of transgenic mice carrying mutated human amyloid precursor protein

Alzheimer's disease transgenic mice overexpressing human amyloid precursor protein (hAPP) with the Swedish double mutation (hAPP(Sw)) develop age-rela ted amyloid deposition and behavioral and electrophysiologic changes by an unknown mechanism. Analysis of glutamatergic receptor subtypes in 4- and 15 -month-old heterozygous hAPP(Sw) transgenic mice revealed a selective incre ase in AMPA receptor binding in the hippocampus of 15-month-old transgenic mice, which have established cortical and hippocampal amyloid deposits. The re were no significant alterations of GluR1, GluR2, and GluR4 protein expre ssion by semiquantitative confocal analysis or GluR1 mRNA by in situ hybrid ization. There was no significant alteration in NMDA, in group I and II met abotropic glutamate and in muscarinic receptor binding, or in striatal dopa mine and adenosine receptor binding in 15-month-old mice. These data sugges t that mutant APP overexpression or age-related amyloid deposition produce a subtle specific alteration in hippocampal glutamate receptors with aging. (C) 2001 Academic Press.