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Molecular Differences and Similarities between Alzheimer's Disease and the 5XFAD Transgenic Mouse Model of Amyloidosis

Maarouf, Chera L., Kokjohn, Tyler A., Whiteside, Charisse M., Macias, MiMi P., Kalback, Walter M., Sabbagh, Marwan N., Beach, Thomas G., Vassar, Robert, Roher, Alex E.·2013·Biochemistry Insights

DOI 10.4137/bci.s13025PMC PMC4154482

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Abstract

Transgenic (Tg) mouse models of Alzheimer's disease (AD) have been extensively used to study the pathophysiology of this dementia and to test the efficacy of drugs to treat AD. The 5XFAD Tg mouse, which contains two presenilin-1 and three amyloid precursor protein (APP) mutations, was designed to rapidly recapitulate a portion of the pathologic alterations present in human AD. APP and its proteolytic peptides, as well as apolipoprotein E and endogenous mouse tau, were investigated in the 5XFAD mice at 3 months, 6 months, and 9 months. AD and nondemented subjects were used as a frame of reference. APP, amyloid-beta (Aβ) peptides, APP C-terminal fragments (CT99, CT83, AICD), β-site APP-cleaving enzyme, and APLP1 substantially increased with age in the brains of 5XFAD mice. Endogenous mouse tau did not show age-related differences. The rapid synthesis of Aβ and its impact on neuronal loss and neuroinflammation make the 5XFAD mice a desirable paradigm to model AD.

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Authors: Maarouf, C. L., Kokjohn, T. A., Whiteside, C. M., Macias, M. P., Kalback, W. M., Sabbagh, M. N., Beach, T. G., Vassar, R., & Roher, A. E.
Affiliations: The Longtine Center for Neurodegenerative Biochemistry, Banner Sun Health Research Institute Sun City, AZ, USA.
Roberts Clinical Center, Banner Sun Health Research Institute Sun City, AZ, USA.
Harold Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, AZ, USA.
Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Venue: Biochemistry Insights
Publisher: SAGE Publications
Published: 2013-01
Volume: 6
Pages: BCI.S13025
ISSN: 1178-6264
DOI: 10.4137/bci.s13025
PMC: PMC4154482
Cited by: 60
References: 64
Language: en
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)

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Molecular Differences and Similarities between Alzheimer's Disease and the 5XFAD Transgenic Mouse Model of Amyloidosis

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