Modeling Functional Limitations, Gait Impairments, and Muscle Pathology in Alzheimer’s Disease: Studies in the 3xTg-AD Mice

Abstract

Frailty; Muscular strength; Translational neuroscience

Fragilidad; Fuerza muscular; Neurociencia traslacional

Fragilitat; Força muscular; Neurociència translacional

Gait impairments in Alzheimer’s disease (AD) result from structural and functional deficiencies that generate limitations in the performance of activities and restrictions in individual’s biopsychosocial participation. In a translational way, we have used the conceptual framework proposed by the International Classification of Disability and Health Functioning (ICF) to classify and describe the functioning and disability on gait and exploratory activity in the 3xTg-AD animal model. We developed a behavioral observation method that allows us to differentiate qualitative parameters of psychomotor performance in animals’ gait, similar to the behavioral patterns observed in humans. The functional psychomotor evaluation allows measuring various dimensions of gait and exploratory activity at different stages of disease progression in dichotomy with aging. We included male 3xTg-AD mice and their non-transgenic counterpart (NTg) of 6, 12, and 16 months of age (n = 45). Here, we present the preliminary results. The 3xTg-AD mice show more significant functional impairment in gait and exploratory activity quantitative variables. The presence of movement limitations and muscle weakness mark the functional decline related to the disease severity stages that intensify with increasing age. Motor performance in 3xTg-AD is accompanied by a series of bizarre behaviors that interfere with the trajectory, which allows us to infer poor neurological control. Additionally, signs of physical frailty accompany the functional deterioration of these animals. The use of the ICF as a conceptual framework allows the functional status to be described, facilitating its interpretation and application in the rehabilitation of people with AD.

This work was funded by 2017-SGR-1468 and UAB-GE-260408 to L.G.-L. The colony of 3xTg-AD mice is sustained by ArrestAD H2020 Fet-OPEN-1-2016-2017-737390, European Union’s Horizon 2020 research and innovation program under grant agreement No 737390 to L.G.-L. It also received financial support from Memorial Mercedes Llort Sender 2021/80/09241941.8.