Clasping, ledge-score coordination and early gait impairments as primary behavioural markers of functional impairment in Alzheimer's disease

Abstract

Motor performance facilitates the understanding of the functional state related to the progression of Alzheimer's disease (AD). At the translational level, this brief report refines the characterization of the motor dysfunction of the 3xTg-AD mouse model in different motor tasks, focusing on the abnormal clasping reflex and coordination impairments measured through the Phenotype Scoring System four items screening originally developed for models of ataxia. We studied male 3xTg-AD mice at 6, 12, and 16 months of age (mimicking the early, advanced, and late stages of the disease, respectively) and their age-matched non-transgenic counterparts with normal aging. According to the score, incidence, or severity of the four items and the total score, the 3xTg-AD mice showed deficiencies in all score elements. Clasping was increased independently of age, and its severity worsened with repeated testing. In contrast, the impairment of coordination worsened with the progress of the disease. The gait score was sensitive to genotype since early stages, and the worse ledge score was evident at 16 months. Kyphosis and ledge scores were sensitive to age. The impairments and functional limitations of male 3xTg-AD mice related to the stages of AD provide a scenario that allows understanding the heterogeneity of non-cognitive symptoms.