期刊
NEUROBIOLOGY OF AGING
卷 34, 期 3, 页码 731-744出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2012.08.006
关键词
Alzheimer's disease; Mouse models; Attention; Response control; Touchscreen; Memory; Cognition; beta-amyloid; TgCRND8
资金
- Alzheimer's Research Trust [ART/ESG2010/1]
- MRC/Wellcome Trust Neurodegenerative Diseases Initiative [WT089703AIA]
- Alzheimers Research UK [ART-ESG2010-1, ART-PG2006-5] Funding Source: researchfish
- Medical Research Council [MC_G1000734, G0001354B, G0001354, G1000183B] Funding Source: researchfish
- MRC [MC_G1000734] Funding Source: UKRI
Transgenic mouse models of Alzheimer's disease (AD) with abundant beta-amyloid develop memory impairments. However, multiple nonmnemonic cognitive domains such as attention and executive control are also compromised early in AD individuals, but have not been routinely assessed in animal models. Here, we assessed the cognitive abilities of TgCRND8 mice-a widely used model of beta-amyloid pathology-with a touch screen-based automated test battery. The test battery comprises highly translatable tests of multiple cognitive constructs impaired in human AD, such as memory, attention, and response control, as well as appropriate control tasks. We found that familial AD mutations affect not only memory, but also cause significant alterations of sustained attention and behavioral flexibility. Because changes in attention and response inhibition may affect performance on tests of other cognitive abilities including memory, our findings have important consequences for the assessment of disease mechanisms and therapeutics in animal models of AD. A more comprehensive phenotyping with specialized, multicomponent cognitive test batteries for mice might significantly advance translation from preclinical mouse studies to the clinic. (C) 2013 Elsevier Inc. All rights reserved.
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