Activity changes and marked stereotypic behavior precede A pathology in TgCRND8 Alzheimer mice

Ambrée, Oliver; Touma, Chadi; Görtz, Nicole; Keyvani, Kathy; Paulus, Werner; Palme, Rupert; Sachser, Norbert

doi:10.1016/j.neurobiolaging.2005.05.009

« Previous Next »Neurobiology of Aging
Volume 27, Issue 7 , Pages 955-964, July 2006

Activity changes and marked stereotypic behavior precede A pathology in TgCRND8 Alzheimer mice

Oliver Ambrée
- Department of Behavioural Biology, University of Münster, Badestr. 9, D-48149 Münster, Germany
- Institute of Neuropathology, University Hospital Münster, Domagkstr. 19, D-48149 Münster, Germany
- Corresponding author. Tel.: +49 251 83 24783; fax: +49 251 83 23896.
Chadi Touma
- Department of Behavioural Biology, University of Münster, Badestr. 9, D-48149 Münster, Germany
- Present address: Max Planck Institute of Psychiatry, Kraepelinstr. 2, D-80804 Munich, Germany.
Nicole Görtz
- Department of Behavioural Biology, University of Münster, Badestr. 9, D-48149 Münster, Germany
Kathy Keyvani
- Institute of Neuropathology, University Hospital Münster, Domagkstr. 19, D-48149 Münster, Germany
Werner Paulus
- Institute of Neuropathology, University Hospital Münster, Domagkstr. 19, D-48149 Münster, Germany
Rupert Palme
- Institute of Biochemistry, University of Veterinary Medicine Vienna, Veterinärplatz 1, A-1210 Vienna, Austria
Norbert Sachser
- Department of Behavioural Biology, University of Münster, Badestr. 9, D-48149 Münster, Germany

Received 2 March 2005; received in revised form 3 May 2005; accepted 11 May 2005. published online 01 July 2005.

Abstract

Alzheimer’s disease (AD) is not only characterized by cognitive decline and neuropathological changes, but also by non-cognitive behavioral symptoms like restlessness, sleep disturbance, and wandering. These symptoms are categorized in the “Behavioral and Psychological Symptoms of Dementia” (BPSD). We investigated transgenic and wildtype mice of an APP transgenic mouse model of AD (TgCRND8) with respect to 24 h activity and spontaneous home cage behavior at 30, 60, 90 and 120 days of age. At all test days, transgenic and wildtype animals differed significantly with respect to activity patterns. In addition, activity rhythms changed distinctly in transgenic mice with increasing age. Transgenic mice also clearly showed more stereotypic behavior, which correlated significantly at 90 and 120 days of age with elevated corticosterone metabolite concentrations in fecal samples. Activity patterns in TgCRND8 mice resemble altered rhythms of activity in AD patients. Stereotypic behaviors may be caused by the same mechanisms as non-cognitive behavioral symptoms of AD. Thus, it is likely that analogies to BPSD that precede A pathology are found in APP-overexpressing TgCRND8 mice.