Systems analysis reveals ageing-related perturbations in retinoids and sex hormones in alzheimer’s and parkinson’s diseases

Simon Lam, Nils Hartmann, Rui Benfeitas, Cheng Zhang, Muhammad Arif, Hasan Turkez, Mathias Uhlén, Christoph Englert, Robert Knight*, Adil Mardinoglu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Neurodegenerative diseases, including Alzheimer’s (AD) and Parkinson’s diseases (PD), are complex heterogeneous diseases with highly variable patient responses to treatment. Due to the growing evidence for ageing-related clinical and pathological commonalities between AD and PD, these diseases have recently been studied in tandem. In this study, we analysed transcriptomic data from AD and PD patients, and stratified these patients into three subclasses with distinct gene expression and metabolic profiles. Through integrating transcriptomic data with a genome-scale metabolic model and validating our findings by network exploration and co-analysis using a zebrafish ageing model, we identified retinoids as a key ageing-related feature in all subclasses of AD and PD. We also demonstrated that the dysregulation of androgen metabolism by three different independent mechanisms is a source of heterogeneity in AD and PD. Taken together, our work highlights the need for stratification of AD/PD patients and development of personalised and precision medicine approaches based on the detailed characterisation of these subclasses.

Original languageEnglish
Article number1310
JournalBiomedicines
Volume9
Issue number10
Early online date24 Sept 2021
DOIs
Publication statusPublished - Oct 2021

Keywords

  • Ageing
  • Alzheimer’s
  • Neurodegeneration
  • Parkinson’s
  • Systems biology

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