Non-cognitive behaviours in an APP/PS1 transgenic model of Alzheimer's disease.
Alzheimer's disease (AD) is characterised by progressive cognitive impairment with neuropsychiatric symptoms such as anomalous motor behaviour, depression, anxiety, weight loss, irritability and agitation. The effect of hAPP and PS1 overexpression on cognition has been well characterised in a variety of transgenic mouse models, however, non-cognitive behaviours have not been considered as systematically. The non-cognitive behaviour of the hAPP/PS1 transgenic mouse model (TASTPM) was observed at ages spanning the rapid progression of amyloid neuropathology. TASTPM transgenic mice, of both genders, exhibited decreased spontaneous motor activity, disinhibition, increased frequency and duration of feeding bouts, reduced body weight and, by 10 months, increased activity over a 24h period. In addition to the aforementioned behaviours, male transgenic mice also displayed enhanced aggression relative to wildtype controls. These data reveal previously unreported disease relevant behavioural changes that demonstrate the value of measuring behaviour in APP/PS1 transgenic models. These behavioural readouts could be useful in screening putative drug treatments for AD.
Pugh
Perdita L
PL
Neurology & GI CEDD, GlaxoSmithKline Research and Development Limited, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK. Pippa_L_Pugh@gsk.com
Richardson
Jill C
JC
Bate
Simon T
ST
Upton
Neil
N
Sunter
David
D
D000367:Age Factors; D000374:Aggression / Q000502:physiology*; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000523:psychology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000502:physiology; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology; D004195:Disease Models, Animal; D005247:Feeding Behavior / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology*; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism*
D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1