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, Karen H. Ashe

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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 APPNLI and tauP301L 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.

Original languageEnglish (US)
Pages (from-to)762-772
Number of pages11
JournalAmerican Journal of Pathology
Volume173
Issue number3
DOIs
StatePublished - Sep 2008

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Neurofibrillary Tangles
Amyloid Plaques
Transgenes
Alzheimer Disease
Pathology
Transgenic Mice
Amyloid beta-Protein Precursor
Tauopathies
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Brain
Gene Expression
Mutation

Cite this

Amyloid plaque and neurofibrillary tangle pathology in a regulatable mouse model of Alzheimer's disease. / Paulson, Jennifer B.; Ramsden, Martin; Forster, Colleen; Sherman, Mathew A.; McGowan, Eileen; Ashe, Karen H.

In: American Journal of Pathology, Vol. 173, No. 3, 09.2008, p. 762-772.

Research output: Contribution to journalArticle

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