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The Journal of Neuroscience, August 15, 2002, 22(16):7218-7224

Compromised Hemodynamic Response in Amyloid Precursor Protein Transgenic Mice

Thomas Mueggler¹, Christine Sturchler-Pierrat², Diana Baumann¹, Martin Rausch¹, Matthias Staufenbiel², and Markus Rudin¹

¹ Central Technologies and ² Nervous System Research, Novartis Pharma, AG, CH-4002 Basel, Switzerland

APP23 transgenic mice overexpressing amyloid precursor protein (APP₇₅₁) reproduce neuropathological changes associated with Alzheimer's disease such as high levels of amyloid plaques, cerebral amyloid angiopathy, and associated vascular pathologies. Functional magnetic resonance imaging (fMRI) was applied to characterize brain functionality in these mice through global pharmacological stimulation. The cerebral hemodynamic response to infusion of the GABA_A antagonist bicuculline was significantly reduced in aged APP23 mice compared with age-matched wild-type littermates. This is in part attributable to a compromised cerebrovascular reactivity, as revealed by the reduced responsiveness to vasodilatory stimulation by acetazolamide. The study shows that fMRI is a sensitive tool to phenotype genetically engineered animals modeling neuropathologies.

Key words: acetazolamide; amyloid precursor protein (APP); -amyloid; transgenic mice; GABA_A antagonist; functional magnetic resonance imaging (fMRI); Ptc_CO2

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22167218-07$05.00/0

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