The deleterious effects of Alzheimer’s disease pathology on skeletal muscle

Abstract

Cognitive dysfunction and skeletal muscle dysfunction tend to coexist, and the combined condition of MCI and physical frailty is defined as cognitive frailty. In this review, to understand the pathomechanism of skeletal muscle dysfunction in Alzheimer’s disease (AD), the most common cause of cognitive impairment, we first describe the physiological functions of Aβ peptide, the causative factor of AD, and its precursor, APP, in skeletal muscle. Next, the mechanism of skeletal muscle dysfunction associated with AD is discussed based on the findings of inclusion body myositis, which shows pathological conditions similar to AD, such as the accumulation of Aβ42. Then, recent findings on the effects of skeletal muscle secretory peptides on AD pathology will be presented and the physiological significance of the brain-skeletal muscle connection will be discussed. Finally, we will present our experimental results on the skeletal muscle phenotype of AD mouse models and discuss the effects of Alzheimer’s disease causative factors on skeletal muscle.