Skeletal muscle fatigue resistance is differentially affected in 8-month-old male and female hAβ-KI mice.

Here, we assess skeletal muscle form and function of the hAβ-KI mouse at 8 and 15 months of age, before and after onset of cognitive decline, through assessment of whole-body lean mass percentage, isolated muscle contraction of the extensor digitorum longus (EDL) and soleus muscle, and fibre type analysis of male and female mice. Whole-body lean mass declined over time in all mice; however, only male hAβ-KI mice had a significant change in body mass and lean mass over the study.

At 8-months-old, the isolated EDL of male hAβ-KI mice fatigued faster than the WT mice, but there were no differences at 15 months-old nor fibre type composition at either age. Alternatively, the isolated EDL and soleus of 8-month-old hAβ-KI female mice fatigued slower compared to the WT mice, and there were no differences at 15 months nor fibre type composition at either age. This preliminary characterization work suggests sex-dependent differences in isolated muscle fatigue prior to cognitive decline in the hAβ-KI mouse model of sporadic AD.