Amyloid plaque and neurofibrillary tangle pathology in a regulatable mouse model of Alzheimer's disease.
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-beta (Abeta) 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 Abeta and 4R0N tau in the brain resulted in the development of three neuropathological features of AD: Abeta 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.
Paulson
Jennifer B
JB
Department of Neurology, University of Minnesota Medical School, 420 Delaware St. SE, Minneapolis, MN 55127, USA.
Ramsden
Martin
M
Forster
Colleen
C
Sherman
Mathew A
MA
McGowan
Eileen
E
Ashe
Karen H
KH
D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001921:Brain / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D016874:Neurofibrillary Tangles / Q000473:pathology*; D058225:Plaque, Amyloid / Q000473:pathology*; D019076:Transgenes; D016875:tau Proteins / Q000235:genetics
D016564:Amyloid beta-Protein Precursor; D016875:tau Proteins