The characterisation of neuropathology and cognitive impairments of Alzheimer’s disease in male mice of 5XFAD model

Abstract

 Alzheimer’s Disease is a prevalent disease leading to progressive irreversible loss of cognitive functions. Despite years of continuing research, the underlying pathogenic pathways have not been established, and no effective cure exists. The 5XFAD transgenic mouse model with five familial Alzheimer’s Disease-related gene mutations is one of the mouse models used both for understanding the nature of the disease and for evaluating therapies. By understanding the pathology development in mouse models, researchers could be better informed in terms of selecting suitable animal models and use the appropriate age group best for answering the research questions. The current study characterised cognitive abilities and biochemical pathologies in male 5XFAD at 4, 6 and 10 months of age. The onset of spatial memory and spatial learning impairments in 5XFAD mice is at 6 months, while both spatial working memory and long-term spatial memory are affected at 10 months. Amyloid plaque pathology was observed in subiculum, entorhinal cortex, and Cornu Ammonis 1- 2 at 4 months, then affecting the remainder of the hippocampus at 6 months. Neuronal loss in subiculum occurred at 6 months, coinciding with the onset of behavioural deficits. Behavioural deficits in 5XFAD display a comparable progression pattern as humans, with an onset age at 6 months. However, disparities in pathology exist between 5XFAD and Alzheimer’s Disease patients. Amyloid plaque deposition and neuronal loss varies in term of areas affected, severity and temporal progression, likely with important functional implications. Thus, additional care must be exercised in interpreting the results of studies using 5XFAD.