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.
| Original language | English |
|---|---|
| Pages (from-to) | 1177-1191 |
| Number of pages | 15 |
| Journal | Journal of Alzheimer's disease : JAD |
| Volume | 72 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 1 Jan 2019 |
Keywords
- 5×FAD mouse
- Alzheimer’s disease
- biomarker
- transcriptional profiling