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Searching For The Causes Of Alzheimer's

An interview with Dr Joanna Collingwood, School of Engineering

Published September 2011

September 21st is World Alzheimer’s Day. Alzheimer’s organisations across the world now take part in promotional and fundraising activities to support people with dementia and their carers. At the University of Warwick, Dr Joanna Collingwood and her team are at the forefront of research into the disease, helped by the purchase of a refurbished cryomicrotome to prepare brain tissue for analysis, thanks to a £10,000 donation to the University.

AlzheimersAround 465,000 people in the UK have a form of dementia. The most common cause of dementia is Alzheimer’s disease, named after the German neurologist Alois Alzheimer who first identified it. According to the Alzheimer’s Society: “dementia is a term used to describe various different brain disorders that have in common a loss of brain function that is usually progressive and eventually severe”. There is currently no cure, and symptoms can include memory loss, mood changes and cognitive impairment. “During the course of the disease, the chemistry and structure of the brain changes, leading to the death of brain cells.”

Currently it’s difficult for doctors to make a clear diagnosis for Alzheimer’s disease. In the early stages the clinical symptoms can be quite ambiguous.

The aim of Dr Collingwood’s research is to find out how and why that happens, and in particular, whether changes in the brain's chemistry can be observed before significant numbers of brain cells die. She initially trained as a physicist, and moved into Alzheimer’s research in 2003 where there was an opportunity to apply standard techniques for the study of magnetic materials to a more complex system: iron in the human brain. This led to a postdoctoral fellowship from the Alzheimer’s Society to research iron in brain disease tissue. Healthy brains require a lot of iron for normal function, but there’s evidence that in Alzheimer’s disease the way iron is managed and stored changes, leading to a potentially damaging environment for some of the brain cells.

“There’s no clear evidence that iron is a primary cause of Alzheimer’s” says Dr Collingwood, “but there are numerous studies linking iron with key features of Alzheimer’s disease. What we’re doing is looking at evidence of iron chemistry changes in the brain which may be contributing to the disease.” Her team is primarily focused on looking at whether iron-related changes can be used as biomarkers, with the potential to use them in diagnosing patients.

Currently it’s difficult for doctors to make a clear diagnosis for Alzheimer’s disease. In the early stages the clinical symptoms can be quite ambiguous. Added to this is the fact that Alzheimer’s is often described as a disorder rather than a disease: it can take various courses in patients, with individuals responding differently to treatment. "Although better markers for Alzheimer’s disease are being developed, usually the confirmation of diagnosis is, sadly, at autopsy,” Dr Collingwood explains. “We are hoping our research will contribute to changing this.”

There are two classic pathological markers in a brain affected by Alzheimer’s. These are tangles inside the neurons in the brain, and the accumulation of amyloid plaques in the spaces between the brain cells. Dr Collingwood is looking at how metals influence the formation of the amyloid plaques, which are primarily made from aggregated protein, and the behaviour of them. How are the protein structures made by aggregating amyloid in the brain affected by the presence of certain metal ions, and are these metals found in the actual plaques deposited in Alzheimer’s disease? She and her collaborators at Keele University published in a 2004 paper their discovery that under in-vitro conditions, iron and aluminium encourage beta-pleated structures (as found in the human amyloid plaques) to form whereas copper and zinc do not. “In subsequent studies, we found strong evidence of iron in a lot of the amyloid plaques in the human Alzheimer’s brain. We have now seen evidence of magnetite in the Alzheimer’s tissue, in an ongoing study with colleagues at University of Florida, as well as in our studies of extracted amyloid plaques. It is possible that the formation of magnetite is associated with changes in iron biochemistry creating a more toxic environment for cells in the brain.”

More recently, in conjunction with colleagues at Keele University, Dr Collingwood has contributed to in-vitro research showing how copper can prevent (and reverse) the formation of amyloid into beta-pleated sheets, and how it can also lead to amyloid forming spherulite structures. Dr Collingwood and colleagues then used the Diamond Light Source synchrotron facility in Oxfordshire to show that copper is associated with spherulite structures in Alzheimer’s brain tissue. This is a new observation in terms of understanding how peptides are affected by copper, and the research is being continued to determine the effect of other metals on spherulite formation.

In Dr Collingwood’s team, much of the research involves analysis of the distribution and form of metal ions in brain tissue from regions affected by Alzheimer’s disease.

In Dr Collingwood’s team, much of the research involves analysis of the distribution and form of metal ions in brain tissue from regions affected by Alzheimer’s disease. Her team use the new cryomicrotome equipment to prepare samples of donated brain tissue in order to examine the metal elements that are present in parts per million or billion. The cryomicrotome allows micrometre-thick sections to be cut for analysis, and helps keep samples pure during their preparation for analysis. It’s a skilled job to use the machine. Its introduction in the department means that a new generation of researchers can be trained in-house, as well as making it possible to prepare samples for collaborative projects.

A key member of Dr Collingwood’s team is Mary Finnegan, holder of an Alzheimer’s Society doctoral grant. Mary is investigating whether the iron content in Alzheimer’s-diseased tissue can be identified via magnetic resonance imaging (MRI), and if this could be used as a biomarker.

Together the team aims to work towards tests that can aid diagnosis of Alzheimer’s, and their experimental observations are contributing to an understanding of how the brain changes in Alzheimer’s disease.

Dr Joanna CollingwoodDr Joanna Collingwood is Assistant Professor, Biomedical and Biological Systems Laboratory in the University of Warwick's School of Engineering.

She trained in materials physics at York and Warwick, and then moved into the field of biomedical engineering, with a particular interest in brain imaging in neurodegenerative disorders. She spent six years working at Keele University (UK) and University of Florida (UK), with fellowship support from the Alzheimer's Society, EPSRC, and RCUK.

Dr Collingwood has strong research links with the Materials Science and Engineering department and the McKnight Brain Institute at University of Florida, and with groups in EPSAM and ISTM at Keele University. She is currently a member of the STFC Science in Society panel, and has chaired the Diamond Light Source User Committee since its formation in 2009.