Activity changes and marked stereotypic behavior precede Abeta pathology in TgCRND8 Alzheimer mice.
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 Abeta pathology are found in APP-overexpressing TgCRND8 mice.
Department of Behavioural Biology, University of Münster, Badestr. 9, D-48149 Münster, Germany. ambree@uni-muenster.de
Oliver
O
Ambrée
Chadi
C
Touma
Nicole
N
Görtz
Kathy
K
Keyvani
Werner
W
Paulus
Rupert
R
Palme
Norbert
N
Sachser
D000313:Adrenal Medulla / Q000378:metabolism / Q000503:physiopathology; D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D002940:Circadian Rhythm / Q000235:genetics*; D003345:Corticosterone / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics*; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013239:Stereotyped Behavior / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D014446:Tyrosine 3-Monooxygenase; D003345:Corticosterone