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

Lam, SimonKings Coll London, Fac Dent Oral & Craniofacial Sci, London SE1 9RT, England. (författare)

QC 20211112
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.

Hartmann, NilsLeibniz Inst Aging Fritz Lipmann Inst, D-07745 Jena, Germany.;Univ Med Ctr, Inst Pathol, D-55131 Mainz, Germany. (författare)
Benfeitas, RuiStockholm Univ, Dept Biochem & Biophys, Sci Life Lab, Natl Bioinformat Infrastruct Sweden NBIS, SE-17121 Stockholm, Sweden.(Swepub:kth)u120u6dr (författare)
Zhang, ChengKTH,Science for Life Laboratory, SciLifeLab,Systembiologi(Swepub:kth)u1ww5kvp (författare)
Arif, MuhammadKTH,Systembiologi,Science for Life Laboratory, SciLifeLab(Swepub:kth)u1vvaean (författare)
Turkez, HasanAtaturk Univ, Fac Med, Dept Med Biol, TR-25240 Erzurum, Turkey. (författare)
Uhlén, MathiasKTH,Science for Life Laboratory, SciLifeLab,Systembiologi(Swepub:kth)u1dulvmw (författare)
Englert, ChristophLeibniz Inst Aging Fritz Lipmann Inst, D-07745 Jena, Germany.;Freidrich Schiller Univ Jena, Inst Biochem & Biophys, D-07745 Jena, Germany. (författare)
Knight, RobertKings Coll London, Fac Dent Oral & Craniofacial Sci, London SE1 9RT, England. (författare)
Mardinoglu, AdilKTH,Science for Life Laboratory, SciLifeLab,Systembiologi,Kings Coll London, Fac Dent Oral & Craniofacial Sci, London SE1 9RT, England.(Swepub:kth)u1t8kmr6 (författare)
Kings Coll London, Fac Dent Oral & Craniofacial Sci, London SE1 9RT, England.Leibniz Inst Aging Fritz Lipmann Inst, D-07745 Jena, Germany.;Univ Med Ctr, Inst Pathol, D-55131 Mainz, Germany. (creator_code:org_t)

Av författaren/redakt...: Lam, Simon; Hartmann, Nils; Benfeitas, Rui; Zhang, Cheng; Arif, Muhammad; Turkez, Hasan; visa fler...; Uhlén, Mathias; Englert, Christo ...; Knight, Robert; Mardinoglu, Adil; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Neurovetenskaper

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