Early and sustained altered expression of aging-related genes in young 3xTg-AD mice

Alzheimer's disease (AD) is a multifactorial neurological condition associated with a genetic profile that is still not completely understood. In this study, using a whole gene microarray approach, we investigated age-dependent gene expression profile changes occurring in the hippocampus of young and old transgenic AD (3xTg-AD) and wild-type (WT) mice. The aim of the study was to assess similarities between aging- and AD-related modifications of gene expression and investigate possible interactions between the two processes. Global gene expression profiles of hippocampal tissue obtained from 3xTg-AD and WT mice at 3 and 12 months of age (m.o.a.) were analyzed by hierarchical clustering. Interaction among transcripts was then studied with the Ingenuity Pathway Analysis (IPA) software, a tool that discloses functional networks and/or pathways associated with sets of specific genes of interest. Cluster analysis revealed the selective presence of hundreds of upregulated and downregulated transcripts. Functional analysis showed transcript involvement mainly in neuronal death and autophagy, mitochondrial functioning, intracellular calcium homeostasis, inflammatory response, dendritic spine formation, modulation of synaptic functioning, and cognitive decline. Thus, overexpression of AD-related genes (such as mutant APP, PS1, and hyperphosphorylated tau, the three genes that characterize our model) appears to favor modifications of additional genes that are involved in AD development and progression. The study also showed overlapping changes in 3xTg-AD at 3 m.o.a. and WT mice at 12 m.o.a., thereby suggesting altered expression of aging-related genes that occurs earlier in 3xTg-AD mice

Interpreting joint moments and powers in gait

Gait analysis is becoming an increasingly important tool to provide a quantitative description of a patient's gait deviations. It is not only used to diagnose walking disorders but also for treatment selection and evaluation. While spatiotemporal, kinematic, and EMG parameters are commonly used to describe movement and muscle activity, kinetic measures are less often evaluated, even though they give insight into the moments and powers that drive human walking. As such, kinetic parameters are able to connect abnormal movement to underlying muscle malfunction and bony malalignment. This chapter focuses on the role of joint moments and powers of the lower extremities in clinical gait analysis. After a brief introduction of normal kinetic patterns, the clinical interpretation of abnormal joint moments and powers is described. Next, typical deviations in lower limb kinetics are illustrated for several patient populations, including stroke, cerebral palsy, Duchenne muscular dystrophy, anterior cruciate ligament (ACL) injury, and osteoarthritis (OA), and for patients walking with prostheses or orthotics. This section also illustrates the clinical usefulness of specific kinetic parameters in these patient populations, including their sensitivity to treatment and ability to predict treatment outcome. The chapter illustrates that the role of kinetics within clinical gait analysis deserves more attention, and potential applications should be further pursued