Circulating, Cell-Free Micro-RNA Profiles Reflect Discordant Development of Dementia in Monozygotic Twins

Article type: Research Article

Authors: Mengel-From, Jonas^{a; b; *} | Rønne, Mette E.^c | Carlsen, Anting L.^c | Skogstrand, Kristin^e | Larsen, Lisbeth A.^a | Tan, Qihua^{a; b} | Christiansen, Lene^a | Christensen, Kaare^{a; b; d} | Heegaard, Niels H.H.^{c; d}

Affiliations: [a] Department of Public Health, The Danish Aging Research Center and The Danish Twin Registry, Epidemiology, Biostatistics and Biodemography Unit, University of Southern Denmark, Odense, Denmark | [b] Department of Clinical Genetics, Odense University Hospital, Odense, Denmark | [c] Department of Autoimmunology and Biomarkers, Statens Serum Institut, Copenhagen, Denmark | [d] Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark | [e] Department of Congenital Disorders, Center for Neonatal Screening, Statens Serum Institut, Copenhagen, Denmark

Correspondence: [*] Correspondence to: Jonas Mengel-From, J.B. Winsløws Vej 9, 5000 Odense C, Denmark. Tel.: +45 6550 4130; Fax: +45 6550 3682; E-mail: [email protected].

Abstract: We aim to examine if circulating micro-RNA and cytokine levels associate with dementia diagnosis and cognitive scores. To test our hypothesis, we use plasma donated from 48 monozygotic twin pairs in 1997 and 46 micro-RNAs and 10 cytokines were quantified using microfluidic RT-qPCR and multiplex solid-phase immunoassays, respectively. Micro-RNA and cytokine profiling were examined for associations with dementia diagnoses in a longitudinal registry study or with cognitive scores at baseline. Thirty-six micro-RNAs and all cytokines were detected consistently. Micro-RNA profiles associate with diagnoses and cognitive scores at statistically significant levels while cytokine only showed trends pointing at chronic inflammation in twins having or developing dementia. The most notable findings were decreased miR-106a and miR-210, and increased miR-106b expression in twins with a dementia diagnosis. This pioneering evaluation of micro-RNA and cytokine and dementia diagnosis suggests micro-RNA targets in vasculogenesis, lipoprotein transport, and amyloid precursor protein genes.

Keywords: Aging, Alzheimer’s disease, brain, genetics, neurodegenerative

DOI: 10.3233/JAD-171163

Journal: Journal of Alzheimer's Disease, vol. 63, no. 2, pp. 591-601, 2018