Photo supplied by: The Florey Institute of Neuroscience and Mental Health
The role of metals in healthy brain ageing—identification of novel compounds to prevent age-related cognitive decline
The Florey Institute of Neuroscience and Mental Health | 2012 | Project Grant | $789,733
Team members: Dr Victoria Perreau, Dr Feng Chen, Ms Krista Dent, Ms Amelia Sedjahtera, Ms Lydia Gunawan, Ms Lisa Bray and Mrs Kali Perronnes.
Impaired memory is one of the most debilitating features of ageing—with little understanding and treatment available. Associate Professor Paul Adlard and his team wanted to understand how zinc is critical for normal cognitive function and how restoring zinc levels in the brain could lead to improved memory as we age.
‘In Australia, 15 per cent of the population are aged 65+, estimated to grow to 21 per cent (8.4 million) by 20501.’
Associate Professor Adlard’s interests in neuroscience are motivated by the plasticity of the brain and the fact that losing brain function does not need to be an inevitable consequence of ageing or neurodegeneration.
‘The brain is not a static organ. I strongly believe that with sufficient knowledge and insight we can harness the brain’s complexity and plasticity to improve its function and promote healthy, happy ageing.’
‘The aged brain remains capable of performing with appropriate intervention. Simple behavioural modifications through to targeted pharmacological interventions can positively impact brain structure and biochemistry, resulting in improved cognition across age and also in disease.’
One of these targeted pharmacological interventions could be through the regulation of zinc—found to play a critical role in regulating communication between brain cells. The highest concentrations of zinc have been found among the brain cells in the hippocampus, one of the key centres of learning and memory in the brain.
‘If there is a deficit in zinc in the hippocampus—resulting from genetic factors, age or disease for example—then it precipitates a decline in cognitive function,’ Associate Professor Adlard said.
‘We tested whether we could pharmacologically restore these metal levels in key regions of the brain required for learning and memory, and subsequently, whether this translated into improved memory.’
Associate Professor Adlard’s main scientific discovery has been that zinc at the synapses—the signalling connection between brain cells—is vital for normal learning and memory. Critically, his team are investigating the use of a targeted therapeutic that restores zinc levels.
‘As this work progresses, it is anticipated that a prototype cognitive therapeutic approach will be developed for clinical translation with our commercial partner,’ he concluded.
Associate Professor Adlard is now looking at how to better target this intervention—finding at the optimal therapeutic approach to achieve prolonged cognitive benefit throughout life. This involves investigating the metal transporters and associated metal-dependent proteins that alter with age. It also involves large scale population approaches to determine whether we can predict cognitive decline by identifying specific variations in metal transporter proteins.
1 Australian Institute of Health and Welfare (2015), Australia’s welfare