E.V. and D.V.D. contributed equally to this work.
Altered circadian locomotor activity in APP23 mice: a model for BPSD disturbances
Article first published online: 25 NOV 2004
European Journal of Neuroscience
Volume 20, Issue 10, pages 2757–2766, November 2004
How to Cite
Vloeberghs, E., Van Dam, D., Engelborghs, S., Nagels, G., Staufenbiel, M. and De Deyn, P. P. (2004), Altered circadian locomotor activity in APP23 mice: a model for BPSD disturbances. European Journal of Neuroscience, 20: 2757–2766. doi: 10.1111/j.1460-9568.2004.03755.x
- Issue published online: 25 NOV 2004
- Article first published online: 25 NOV 2004
- Received 15 June 2004, revised 9 August 2004, accepted 22 September 2004
- activity disturbances;
- Alzheimer's disease;
- cage activity recording;
- transgenic mouse model;
Over the past decade, clinical Alzheimer's disease research has been challenged with an increased interest in noncognitive symptomatology, commonly referred to as behavioural and psychological signs and symptoms of dementia (BPSD). In accordance, major attention is being paid to behavioural alterations in the phenotyping of transgenic mouse models. Besides an age-dependent decline of cognitive functions, the APP23 model was previously shown to exhibit cage activity disturbances, reminiscent of diurnal rhythm disturbances in Alzheimer patients. To further scrutinize these observations, circadian patterns of horizontal locomotor activity were assessed in 3-, 6- and 12-month-old APP23 mice and wild-type littermates in a test paradigm continuously recording cage activity over a period ranging from 1 to 3 days. At the age of 3 months, APP23 profiles resembled the wild-type pattern to a large extent, although minor differences were already noticeable. Six-month-old APP23 mice displayed an altered activity profile with a first indication of increased activity during the second half of the active phase, reminiscent of sundowning behaviour in Alzheimer patients. This bimodal overnight activity pattern became even more evident at the age of 12 months. The APP23 model was therefore shown to display an age-dependent development of cage activity disturbances and sundowning-like behaviour. A comparison is made with actigraphic recordings of human Alzheimer patients exhibiting sundowning behaviour. This first report of diurnal rhythm disturbances and sundowning-like phenomena in a transgenic mouse model greatly adds to the validity of the APP23 model.