Frailty index and phenotype frailty score: Sex- and age-related differences in 5XFAD transgenic mouse model of Alzheimer’s disease

Alzheimer's disease patients (AD), as well as AD transgenic mice, are characterized by increased frailty. Furthermore, the assessment of frailty status represents a feasible approach for detecting individuals prone to develop more severe form of AD and for measuring the outcome of existing and putative AD therapeutics. The 5xFAD mouse is one of the widely used transgenic animal models of AD, but frailty in this model is scantly investigated. We used two validated mouse frailty assessment tools: phenotypic frailty score (FS) and clinical frailty index (FI) to investigate age- and sex- related differences in frailty status in 5xFAD mice. These tools measure different age-related deficits and do not necessarily identify the same subpopulations as frail. We detected a significant increase in frailty with age in both sexes, although females were surprisingly less frail than males. Depending on the tools used, a notable difference in frailty status was detected, with frailty index and frailty score identifying different mice as frail. These results warrant great caution when choosing the frailty tool and point to the need for further adaptation of frailty measurements in mouse models of AD.