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Systems Analysis Reveals Ageing-Related Perturbations in Retinoids and Sex Hormones in Alzheimer's and Parkinson's Diseases
Kings Coll London, Fac Dent Oral & Craniofacial Sci, London SE1 9RT, England..ORCID iD: 0000-0002-4476-0971
Leibniz Inst Aging Fritz Lipmann Inst, D-07745 Jena, Germany.;Univ Med Ctr, Inst Pathol, D-55131 Mainz, Germany..
Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, Natl Bioinformat Infrastruct Sweden NBIS, SE-17121 Stockholm, Sweden..ORCID iD: 0000-0001-7972-0083
KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology.ORCID iD: 0000-0002-3721-8586
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2021 (English)In: Biomedicines, E-ISSN 2227-9059, Vol. 9, no 10, article id 1310Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
MDPI AG , 2021. Vol. 9, no 10, article id 1310
Keywords [en]
neurodegeneration, Alzheimer's, Parkinson's, ageing, systems biology
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:kth:diva-304753DOI: 10.3390/biomedicines9101310ISI: 000711745500001PubMedID: 34680427Scopus ID: 2-s2.0-85116067057OAI: oai:DiVA.org:kth-304753DiVA, id: diva2:1611046
Note

QC 20211112

Available from: 2021-11-12 Created: 2021-11-12 Last updated: 2024-03-15Bibliographically approved

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Benfeitas, RuiZhang, ChengArif, MuhammadUhlén, MathiasMardinoglu, Adil

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Lam, SimonBenfeitas, RuiZhang, ChengArif, MuhammadUhlén, MathiasKnight, RobertMardinoglu, Adil
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