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Alzheimer's disease transgenic mice overexpressing human amyloid precursor protein (hAPP) with the Swedish double mutation (hAPP(Sw)) develop age-related 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(More)
BACKGROUND Allosteric modulation of γ-secretase is an attractive therapeutic approach for the treatment of Alzheimer's disease. We recently identified a novel γ-secretase modulator, GSM-10h, which effectively lowers Aβ42 production in cells and in amyloid precursor protein transgenic mice. OBJECTIVE Here, we describe the in vivo characterization of(More)
Epilepsy is a disease of recurrent seizures that can develop after a wide range of brain insults. Although surgical resection of focal regions of seizure onset can result in clinical improvement, the molecular mechanisms that produce and maintain focal hyperexcitability are not understood. Here, we demonstrate a regional, persistent induction of a common(More)
BACKGROUND Cleavage of the amyloid precursor protein (APP) by β-site APP-cleaving enzyme and γ-secretase results in the generation of amyloid-β (Aβ) peptides that aggregate and deposit as senile plaques in brains of Alzheimer disease patients. Due to the fundamental role γ-secretase plays in the proteolysis of a number of proteins including Notch,(More)
BACKGROUND cDNA microarrays are a powerful means to screen for biologically relevant gene expression changes, but are often limited by their ability to detect small changes accurately due to "noise" from random and systematic errors. While experimental designs and statistical analysis methods have been proposed to reduce these errors, few studies have(More)
The use of transgenic models in scientific research has made an enormous contribution to our understanding of the causes and symptoms of many diseases, including neurodegenerative conditions such as Alzheimer's Disease (AD) and Parkinson's Disease (PD). In the creation of transgenic models of neurodegenerative disease, effects of the background strain of(More)
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