Fine Motor Function Deficits in the 5xFAD Mouse Model of Alzheimer’s Disease

Alzheimer's disease (AD) involves not only progressive memory and cognition deficits but also motor impairments, including disturbed balance and activity levels and gait dysfunction. We examined age-related changes in fine motor skills of an Alzheimer's mouse model, the transgenic 5xFAD, from 3 to 9 months of age (3M, 9M), using a battery of behavioral tests including the rotarod for motor coordination and balance, balance beam test for fine motor precision and coordination, and single-pellet reaching test for forelimb dexterity. Rotarod test showed that 9M 5xFAD mice displayed mild motor coordination deficits, spending less time on the rod and falling at lower speeds than 9M WT mice. In the balance beam test, 9M 5xFAD mice exhibited significantly slower traversal times compared to other groups and demonstrated frequent foot slips and dragging behavior with more pronounced effects on the narrower beam. The single-pellet reaching test revealed impaired fine limb movements in 9M 5xFAD mice, with reduced success rates and slower speed than the other groups. This study showed that 9M 5xFAD mice exhibited the most impaired performance at each assay in an age-dependent manner, suggesting that the accumulation of the underlying AD-related pathology affects motor function, extending even to fine motor skills.