Affiliations: [a] Wolfson Centre for Age-Related Diseases, King’s College London, London Bridge, London, UK
| [b] College of Medicine and Health, University of Exeter, Exeter, UK
Correspondence:
[*]
Correspondence to: Gareth Williams, Wolfson Centre for Age-Related Diseases, King’s College London, London Bridge, London SE1 1UL, UK. E-mail: gareth.2.williams@kcl.ac.uk.
Abstract: Background:Alzheimer’s disease (AD) is an incurable complex neurodegenerative condition with no new therapies licensed in the past 20 years. AD progression is characterized by the up- and downregulation of distinct biological processes that can be followed through the expression level changes of associated genes and gene networks. Objective:Our study aims to establish a multiplex gene expression tracking platform to follow disease progression in an animal model facilitating the study of treatment paradigms. Methods:We have established a multiplex platform covering 47 key genes related to immunological, neuronal, mitochondrial, and autophagy cell types and processes that capture disease progression in the 5×FAD mouse model. Results:We show that the immunological response is the most pronounced change in aged 5×FAD mice (8 months and above), and in agreement with early stage human disease samples, observe an initial downregulation of microglial genes in one-month-old animals. The less dramatic downregulation of neuronal and mitochondrial gene sets is also reported. Conclusion:This study provides the basis for a quantitative multi-dimensional platform to follow AD progression and monitor the efficacy of treatments in an animal model.
