Cognitive deficits in single App knock in mouse models
Transgenic mouse models of Alzheimer's disease (AD) with nonphysiologic overexpression of amyloid precursor protein (APP) exhibit various unnatural symptoms/dysfunctions. To overcome this issue, mice with single humanized App knock in (KI) carrying Swedish (NL) Beyreuther/Iberian (F) and Arctic (G) mutations in different combinations were recently developed. The validity of these mouse models of AD from a behavioral viewpoint, however, has not been extensively evaluated. Thus, using an automated behavior monitoring system, we analyzed various behavioral domains, including executive function, and learning and memory. The App KI mice carrying NL G F mutations showed clear deficits in spatial memory and flexible learning, enhanced compulsive behavior, and reduced attention performance. Mice carrying NL F mutations exhibited modest abnormalities. The NL G F mice had a greater and more rapid accumulation of Ab deposits and glial responses. These findings reveal that single pathologic App KI is sufficient to produce deficits in broad cognitive domains and that App KI mouse lines with different levels of pathophysiology are useful models of AD.
Neurobiology of Learning and Memory