Published online before print July 31, 2008

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(American Journal of Pathology. 2008;173:762-772.)
© 2008 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2008.080175

Amyloid Plaque and Neurofibrillary Tangle Pathology in a Regulatable Mouse Model of Alzheimer’s Disease

Jennifer B. Paulson^*, Martin Ramsden^*, Colleen Forster, Mathew A. Sherman^*, Eileen McGowan and Karen H. Ashe^*

From the Departments of Neurology^* and Laboratory Medicine and Pathology, University of Minnesota, Medical School, Minneapolis, Minnesota; the Geriatric Research Education and Clinical Center, Veterans Administration Medical Center, Minneapolis, Minnesota; and the Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, Florida

Transgenic mouse models that independently express mutations in amyloid precursor protein (APP) and tau have proven useful for the study of the neurological consequences of amyloid-β (Aβ) plaque and neurofibrillary tangle pathologies. Studies using these mice have yielded essential discoveries with regard to specific aspects of neuronal dysfunction and degeneration that characterize the brain during Alzheimer’s disease (AD) and other age-dependent tauopathies. Most recent transgenic studies have focused on the creation of regulatable models that allow the temporal control of transgene expression. To study a more complete model of AD pathology, we designed a new regulatable transgenic mouse that harbors both APP and tau transgenes. Here, we present a novel transgenic mouse model, rTg3696AB, which expresses human APP_NLI and tau_P301L driven by the CaMKII promoter system. Subsequent generation of Aβ and 4R0N tau in the brain resulted in the development of three neuropathological features of AD: Aβ plaques, neurofibrillary tangles, and neurodegeneration. Importantly, transgene expression in these mice is regulatable, permitting temporal control of gene expression and the investigation of transgene suppression.