Co-Expression Analysis of microRNAs and Proteins in Brain of Alzheimer’s Disease Patients
Callum N. Watson,
Ghazala Begum,
Emma Ashman,
Daniella Thorn,
Kamal M. Yakoub,
Moustafa Al Hariri,
Ali Nehme,
Stefania Mondello,
Firas Kobeissy,
Antonio Belli,
Valentina Di Pietro
Affiliations
Callum N. Watson
Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Ghazala Begum
Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Emma Ashman
Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Daniella Thorn
Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Kamal M. Yakoub
Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Moustafa Al Hariri
Department of Emergency Medicine, American University of Beirut Medical Center, Beirut 1107 2020, Lebanon
Ali Nehme
Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Stefania Mondello
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98165 Messina, Italy
Firas Kobeissy
Program for Neurotrauma, Neuroproteomics & Biomarkers Research, Departments of Emergency Medicine, Psychiatry, Neuroscience and Chemistry, University of Florida, Gainesville, FL 32611, USA
Antonio Belli
Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Valentina Di Pietro
Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Alzheimer’s disease (AD) is the most common form of dementia globally; however, the aetiology of AD remains elusive hindering the development of effective therapeutics. MicroRNAs (miRNAs) are regulators of gene expression and have been of growing interest in recent studies in many pathologies including AD not only for their use as biomarkers but also for their implications in the therapeutic field. In this study, miRNA and protein profiles were obtained from brain tissues of different stage (Braak III-IV and Braak V-VI) of AD patients and compared to matched controls. The aim of the study was to identify in the late stage of AD, the key dysregulated pathways that may contribute to pathogenesis and then to evaluate whether any of these pathways could be detected in the early phase of AD, opening new opportunity for early treatment that could stop or delay the pathology. Six common pathways were found regulated by miRNAs and proteins in the late stage of AD, with one of them (Rap1 signalling) activated since the early phase. MiRNAs and proteins were also compared to explore an inverse trend of expression which could lead to the identification of new therapeutic targets. These results suggest that specific miRNA changes could represent molecular fingerprint of neurodegenerative processes and potential therapeutic targets for early intervention.
