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The Journal of Neuroscience, September 10, 2003, 23(23):8231-8236

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Age-Dependent Impairment of Somatosensory Response in the Amyloid Precursor Protein 23 Transgenic Mouse Model of Alzheimer's Disease

Thomas Mueggler,¹ Diana Baumann,¹ Martin Rausch,¹ Matthias Staufenbiel,² and Markus Rudin¹

¹Analytical and Imaging Sciences and ²Nervous System Research, Novartis Institute for Biomedical Research, CH-4002 Basel, Switzerland

Quantitative functional magnetic resonance imaging was applied to characterize brain function in amyloid precursor protein 23 (APP23) transgenic mice, which reproduce the neuropathological alterations associated with Alzheimer's disease. Electrical stimulation of the paw led to cerebral blood volume increases in the contralateral somatosensory cortex. In APP23 mice this hemodynamic response decreased with increasing age of the animal and with increasing stimulus amplitude as compared with wild-type animals. The age-dependent dysfunction in APP23 mice may be attributed in part to a compromised cerebrovascular reactivity. Quantitative functional brain mapping that uses standardized sensory inputs should allow for assessment of disease progression and therapy response (e.g., passive immunization against -amyloid) in patients also.

Key words: Alzheimer's disease; amyloid precursor protein; APP; functional magnetic resonance imaging; fMRI; relative cerebral blood volume; transgenic mice; somatosensory cortex; peripheral stimulation; hindpaw; transcutaneous blood gas monitoring

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Received April 3, 2003; revised June 13, 2003; accepted June 25, 2003.

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