[Fundamental study of memory impairment and non-cognitive behavioral alterations in APPswe/PS1dE9 mice].
In addition to cognitive decline, Alzheimer's disease patients also exhibit non-cognitive symptoms commonly referred to as behavioral and psychological symptoms of dementia, or BPSD. These symptoms have a serious impact on the quality of life of these patients, as well as that of their caregivers, but there are currently no effective therapies. The amyloid β-peptide (Aβ) is suspected to play a central role in the cascade leading to Alzheimer's disease, but the precise mechanisms are still incompletely known. To assess the influence of Aβ pathology on cognitive and non-cognitive behaviors, we examined locomotor activity, motor coordination, and spatial memory in male and female APPswePS1dE9 mice (Alzheimer's disease model, double transgenic mice expressing an amyloid precursor protein with Swedish mutation and a presenilin-1 with deletion of exon 9) at 5 months of age, when the mice had subtle Aβ deposits, and again at 9 months of age, when the mice had numerous Aβ deposits. Compared to wild-type mice, the male and female APPswe/PS1dE9 mice showed normal motor coordination in the rotarod test at both 5 and 9 months. In the Morris water maze test, male and female APPswe/PS1dE9 mice showed impaired spatial memory at 9 months; however, no such deficits were found at 5 months. In a locomotor activity test, male APPswe/PS1dE9 mice exhibited locomotor hyperactivity at 9 months, while females exhibited locomotor hyperactivity at both 5 and 9 months compared to the control mice. Together, these results indicate that APPswe/PS1dE9 mice developed spatial memory impairment and BPSD-like behavioral alterations resulting from Aβ accumulation.
Department of Neuroscience for Drug Discovery, Graduate School of Pharmaceutical Sciences, Kyoto University.
Nobuhiko
N
Taniuchi
Tetsuhiro
T
Niidome
Hachiro
H
Sugimoto
D000544:Alzheimer Disease / Q000150:complications*; D000818:Animals; D001522:Behavior, Animal; D003072:Cognition Disorders / Q000209:etiology; D004195:Disease Models, Animal; D005260:Female; D020233:Gait Disorders, Neurologic / Q000209:etiology*; D008297:Male; D008569:Memory Disorders / Q000209:etiology*; D051379:Mice