This project will investigate the role of iron in brain ageing and provide insight into its influence on neurodegeneration and cognitive decline. The accumulation of iron in the brain has become an established hallmark of ageing (Ashraf 2018, Ward 2014) with selective accumulation occurring in several distinct brain areas. Iron accumulation due to iron dyshomeostasis has been reported in a number of neurodegenerative diseases with increased iron reported in the substantia nigra in patients with Parkinson’s Disease and high concentrations of iron present in the insoluble amyloid plaques characteristic of Alzheimer’s Disease. With the advent of magnetic resonance imaging (MRI) based measures of iron deposition it has become possible to map iron concentration in the brain non-invasively on a millimetre scale.
Iron is necessary in a number of important biological processes in the brain including oxygen transport, myelin synthesis and neurotransmitter synthesis and metabolism. Iron levels in the brain can be altered by circulating iron levels and nutrition. Circulating blood is separated from the brain by two barriers: the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) via the choroid plexus. Iron is transported across these barriers by a complex array of different molecules including transferrin.
We aim to establish the link between MRI detected brain iron concentration and brain ageing in the Aberdeen Children of the Nineteen Fifties (ACONF) an existing richly phenotyped imaging, cognitive and early life dataset. Along with first degree relatives, 567 have undergone detailed cognitive, emotional, and multimodal brain MRI. Detailed metal health, longitudinal cognitive trajectories, inflammation, DNA and RNA have already been extracted from this study. Our primary objective is to estimate in-vivo brain iron concentration from multi-echo gradient-echo Quantitative Susceptibility Maps (Acosta-Cabronero, Milovic et al. 2018, Kim, Park et al. 2017) to elucidate the role that iron deposition has in brain ageing. We will combine this with rich life-course data and childhood intelligence to identify those regions that may be responsible for providing resilience or vulnerability to neurodegeneration. This multidisciplinary approach will give unique insight into the direct and indirect influence of iron deposition on brain structure and function, and the resultant consequences for neurodegeneration.
The data generated by this study will clarify the role of brain iron deposition in healthy ageing and may identify contributing factors to current models of neurodegeneration and cognitive decline. Improved precision in diagnosis, therapy monitoring and drug development through a clinical imaging biomarker based on brain iron concentration will have an impact on patient health and will bring a new understanding of the mechanisms of ageing, the pathways that lead to cognitive decline and new ways to diagnose neurodegeneration.
This project is fully integrated within the University of Aberdeen’s Brain Imaging Group (https://www.abdn.ac.uk/ims/research/abic/index.php), which has a long and distinguished record investigating the mechanisms of ageing, in particular the impacts of social, economic and health factors on cognitive decline through the application of computational neuroimaging techniques.
This project is advertised in relation to the research areas of MEDICAL SCIENCES. Formal applications can be completed online: https://www.abdn.ac.uk/pgap/login.php. You should apply for Degree of Doctor of Philosophy in Medical Sciences, to ensure that your application is passed to the correct person for processing.
NOTE CLEARLY THE NAME OF THE SUPERVISOR AND EXACT PROJECT TITLE ON THE APPLICATION FORM.
Candidates should contact the lead supervisor to discuss the project in advance of submitting an application, as supervisors will be expected to provide a letter of support for suitable applicants. Candidates will be informed after the application deadline if they have been shortlisted for interview. Interviews are expected to take place on 23rd or 24th July 2019.
ACOSTA-CABRONERO, J., MILOVIC, C., MATTERN, H., TEJOS, C., SPECK, O. and CALLAGHAN, M.F., 2018. A robust multi-scale approach to quantitative susceptibility mapping. NeuroImage, 183, pp. 7-24.
ASHRAF, A., CLARK, M. and SO, P.-., 2018. The aging of iron man. Frontiers in Aging Neuroscience, 10(MAR),.
KIM, H.-., PARK, S., RHEE, H.Y., LEE, K.M., RYU, C.-., RHEE, S.J., LEE, S.Y., WANG, Y. and JAHNG, G.-., 2017. Quantitative susceptibility mapping to evaluate the early stage of Alzheimer's disease. NeuroImage: Clinical, 16, pp. 429-438.
WARD, R.J., ZUCCA, F.A., DUYN, J.H., CRICHTON, R.R., ZECCA, L.; 2014 The role of iron in brain ageing and neurodegenerative disorders. The Lancet Neurology, 13 (10), pp. 1045-1060.