P.094 The three sisters of fate: Genetics, pathophysiology and outcomes of animal models of neurodegenerative diseases

Abstract

Background: Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease are neurodegenerative disorders characterized by progressive structural and functional loss of specific neuronal populations, protein aggregation, insidious adult onset, and chronic progression. Modeling these diseases in animal models is useful for studying the relationship between neuronal dysfunction and abnormal behaviours and for screening therapies. Methods: We conducted a comprehensive descriptive review of the numerous animal models currently available to study these three diseases with a focus on their utilities and limitations. Results: A vast range of genetic and toxin-induced models have been generated. Our review outlines how these models differ with regards to the genetic manipulation or toxin used and the brain regions lesioned, describes the extent to which they mimic the neuropathological and behavioral deficits seen in the human conditions, and discusses the advantages and drawbacks of each model. Conclusions: We recommend the adoption of a conservative approach when extrapolating findings based on a single animal model and the validation of findings using multiple models. Investing in additional preclinical studies before embarking on more expensive human trials will improve our understanding of the neuropathology underlying neuronal demise and enhance the chances of identifying effective therapies.