Abstract
Mouse models of human diseases are invaluable tools for studying pathogenic mechanisms and testing interventions and therapeutics. For disorders such as Alzheimer’s disease in which numerous models are being generated, a challenging first step is to identify the most appropriate model and age to effectively evaluate new therapeutic approaches. Here we conducted a detailed phenotypic characterization of the 5xFAD model on a congenic C57BL/6 J strain background, across its lifespan – including a seldomly analyzed 18-month old time point to provide temporally correlated phenotyping of this model and a template for characterization of new models of LOAD as they are generated. This comprehensive analysis included quantification of plaque burden, Aβ biochemical levels, and neuropathology, neurophysiological measurements and behavioral and cognitive assessments, and evaluation of microglia, astrocytes, and neurons. Analysis of transcriptional changes was conducted using bulk-tissue generated RNA-seq data from microdissected cortices and hippocampi as a function of aging, which can be explored at the MODEL-AD Explorer and AD Knowledge Portal. This deep-phenotyping pipeline identified novel aspects of age-related pathology in the 5xFAD model.
Highlights
Background & SummaryAnimal models of Alzheimer’s disease play a pivotal role in facilitating our understanding of disease mechanism and for drug discovery
Several factors likely underlie these translational failures, but two prominent reasons are that the vast majority of AD animal models are based on overexpression and the inclusion of autosomal dominant mutations, despite the fact overexpression or genetic mutations do not occur in the overwhelming majority of human AD cases
Www.nature.com/scientificdata objective requires a multiprong strategy, including, in addition to the generation of models more aligned with late-onset Alzheimer’s disease (LOAD), the detailed development of a standardized characterization of a phenotyping pipeline that can provide comprehensive comparative data about molecular, cellular and functional changes that occur as a function of age and brain region
Summary
Background & SummaryAnimal models of Alzheimer’s disease play a pivotal role in facilitating our understanding of disease mechanism and for drug discovery. (c) Time course for theta-burst induced LTP shows that the level of potentiation is reduced in slices from 8 months old 5xFAD mice relative to WT controls.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
