PS-B10-11: PATHOPHYSIOLOGICAL STUDY OF COGNITIVE FRAILTY USING A MOUSE MODEL OF ALZHEIMER'S DISEASE

Abstract

Objective: Hypertension is known to increase the risk of developing dementia including Alzheimer's disease (AD). The concept of cognitive frailty or motoric cognitive risk syndrome, representing a coexistence of physical and cognitive decline, has been attracting attention in the global aging society. However, the molecular mechanisms underlying the pathological interplay between these conditions remain largely unknown. Methods: We investigated the effects of AD pathogenesis on skeletal muscle by using APP23 mice, a mouse model of AD. Three-month-old male APP23 mice and wild-type mice from the same litter were evaluated for skeletal muscle function by grip strength, for cognitive function by passive avoidance and open field tests, and for glucose tolerance and 24-hour voluntary locomotion using a running wheel as factors related to both skeletal muscle function and cognitive function. After dissection, various organs, mainly skeletal muscle, were harvested and wet weight was evaluated. Results: Grip strength and some skeletal muscle weights of APP23 mice were lower than those of wild-type mice. The ipGTT was used to assess glucose tolerance, and the passive avoidance test and open field test were used to assess cognitive function, but there were no significant differences between genotypes. In the running wheel test, which measures voluntary locomotion, APP23 mice were significantly more active than wild-type mice suggesting that the muscle weakness in APP23 mice was not due to disuse. Conclusions: This study demonstrates that APP23 mice exhibit skeletal muscle deficits, including muscle weakness, along with cognitive dysfunction. In addition, APP23 mice showed behavioral abnormalities such as increased voluntary locomotion, which should contribute to increased skeletal muscle function, but skeletal muscle function was conversely decreased, suggesting that the effect of AD on skeletal muscle function is mediated by factors other than behavioral abnormalities due to cognitive dysfunction.