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Changes in amyloid-beta and tau in the cerebrospinal fluid of transgenic mice overexpressing amyloid precursor protein

Maia, LF and Kaeser, SA and Reichwald, J and Hruscha, M and Martus, P and Staufenbiel, M and Jucker, M (2013) Changes in amyloid-beta and tau in the cerebrospinal fluid of transgenic mice overexpressing amyloid precursor protein. Science Translational Medicine.

Abstract

Altered concentrations of amyloid-b (Ab) peptide and Tau protein in the cerebrospinal fluid (CSF) are thought to be predictive markers for Alzheimer's disease (AD). Transgenic mice overexpressing human amyloid precursor protein (APP) have been used to model Ab pathology, but concomitant changes in Ab and Tau in CSF have been less well studied. We measured Ab and Tau in the brains and CSF of two well-characterized transgenic mouse models of AD: one expressing human APP carrying the Swedish mutation (APP23) and the other expressing mutant human APP and mutant human presenilin-1 (APPPS1). Both mouse models exhibit Ab deposition in the brain, but with different onset and progression trajectories. We found an age-related 50 to 80% decrease in Ab42 peptide in mouse CSF and a smaller decrease in Ab40, both inversely correlated with the brain Ab load. Surprisingly, the same mice showed a threefold increase in total endogenous murine Tau in CSF at the stages when Ab pathology became prominent. The results mirror the temporal sequence and magnitude of Ab and Tau changes in the CSF of patients with sporadic and dominantly inherited AD. This observation indicates that APP transgenic mice may be useful as a translational tool for predicting changes in Ab and Tau markers in the CSF of AD patients. These findings also suggest that APP transgenic mouse models may be useful in the search for new disease markers for AD

Item Type: Article
Additional Information: pubid: 44 nvp_institute: NIBR contributor_address: (Maia, Kaeser, Hruscha, Jucker) Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tubingen, D-72076 Tubingen, Germany (Maia, Kaeser, Hruscha, Jucker) German Center for Neurodegenerative Diseases (DZNE), D-72076 Tubingen, Germany (Maia) Department of Neurology, Hospital de Santo Antonio-CHP, 4099-001 Porto, Portugal (Reichwald, Staufenbiel) Novartis Institutes for Biomedical Research, Neuroscience Discovery Basel, CH-4056 Basel, Switzerland (Martus) Institute of Medical Biometry, University of Tubingen, D-72076 Tubingen, Germany
Date Deposited: 13 Oct 2015 13:13
Last Modified: 13 Oct 2015 13:13
URI: https://oak.novartis.com/id/eprint/21892

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