Systems Analysis Reveals Ageing-Related Perturbations in Retinoids and Sex Hormones in Alzheimer’s and Parkinson’s Diseases

ORCID
0000-0002-4476-0971
Affiliation
Faculty of Dentistry, Oral and Craniofacial Sciences, King’s College London, London SE1 9RT, UK; simon.1.lam@kcl.ac.uk
Lam, Simon;
Affiliation
Leibniz Institute on Aging-Fritz Lipmann Institute, 07745 Jena, Germany; nils.hartmann@unimedizin-mainz.de (N.H.); christoph.englert@leibniz-fli.de (C.E.)
Hartmann, Nils;
ORCID
0000-0001-7972-0083
Affiliation
National Bioinformatics Infrastructure Sweden (NBIS), Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, SE-17121 Stockholm, Sweden; rui.benfeitas@scilifelab.se
Benfeitas, Rui;
ORCID
0000-0002-3721-8586
Affiliation
Science for Life Laboratory, KTH—Royal Institute of Technology, SE-17121 Stockholm, Sweden; cheng.zhang@scilifelab.se (C.Z.); muhammad.arif@scilifelab.se (M.A.); mathias.uhlen@scilifelab.se (M.U.)
Zhang, Cheng;
ORCID
0000-0003-2261-0881
Affiliation
Science for Life Laboratory, KTH—Royal Institute of Technology, SE-17121 Stockholm, Sweden; cheng.zhang@scilifelab.se (C.Z.); muhammad.arif@scilifelab.se (M.A.); mathias.uhlen@scilifelab.se (M.U.)
Arif, Muhammad;
Affiliation
Department of Medical Biology, Faculty of Medicine, Atatürk University, 25240 Erzurum, Turkey; hasanturkez@gmail.com
Turkez, Hasan;
Affiliation
Science for Life Laboratory, KTH—Royal Institute of Technology, SE-17121 Stockholm, Sweden; cheng.zhang@scilifelab.se (C.Z.); muhammad.arif@scilifelab.se (M.A.); mathias.uhlen@scilifelab.se (M.U.)
Uhlén, Mathias;
GND
172568498
ORCID
0000-0002-5931-3189
Affiliation
Leibniz Institute on Aging-Fritz Lipmann Institute, 07745 Jena, Germany; nils.hartmann@unimedizin-mainz.de (N.H.); christoph.englert@leibniz-fli.de (C.E.)
Englert, Christoph;
Affiliation
Faculty of Dentistry, Oral and Craniofacial Sciences, King’s College London, London SE1 9RT, UK; simon.1.lam@kcl.ac.uk
Knight, Robert;
ORCID
0000-0002-4254-6090
Affiliation
Faculty of Dentistry, Oral and Craniofacial Sciences, King’s College London, London SE1 9RT, UK; simon.1.lam@kcl.ac.uk
Mardinoglu, Adil

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.

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