PT  - JOURNAL ARTICLE
AU  - Simon Lam
AU  - Nils Hartmann
AU  - Rui Benfeitas
AU  - Cheng Zhang
AU  - Muhammad Arif
AU  - Hasan Turkez
AU  - Mathias Uhlén
AU  - Christoph Englert
AU  - Robert Knight
AU  - Adil Mardinoglu
TI  - Systems analysis reveals ageing-related perturbations in retinoids and sex hormones in Alzheimer’s and Parkinson’s diseases
AID  - 10.1101/2021.06.10.447367
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.06.10.447367
4099  - http://biorxiv.org/content/early/2021/06/10/2021.06.10.447367.short
4100  - http://biorxiv.org/content/early/2021/06/10/2021.06.10.447367.full
AB  - Neurodegenerative diseases (NDDs), 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 analyse transcriptomic data from AD and PD patients, and stratify 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 identify retinoids as a key ageing-related feature in all subclasses of AD and PD. We also demonstrate 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.Competing Interest StatementThe authors have declared no competing interest.