Lead Investigator: Dr Robert Williams
Institution: University of Bath
Grant type: PhD
Amount: £30,000 (joint funded with MRC)
Start date: October 2010
Completion date: March 2014
Scientific Title: Flavonoids as neuroprotective agents and as regulators of amyloid precursor protein processing: a possible dietary intervention for Alzheimer's Disease?
What was the project, and what did the researchers do?
Like other diseases, such as cancer and type 2 diabetes, environment and lifestyle are thought to have an impact on the likelihood of developing Alzheimer's disease. We regularly hear about studies that make suggestions that increased intake of certain fruits, vegetables and drinks can reduce the risk of developing Alzheimer's.
This PhD project has looked at the effect of a type of chemical called flavonoids (often found in found in plant foods such as dark chocolate, citrus fruit, tea and wine) on the production of protein called amyloid-beta – this protein clumps together in Alzheimer's disease to form the plaques that are a hallmark of the condition.
What were the key results, and how will this help in the fight against dementia?
A subfamily of flavonoids called flavanols, were found to reduce amyloid-beta production in healthy brain cells. The next step was to investigate how they produced this effect.
Although the exact mechanism has not yet been established, it appears flavonoids are lowering amyloid-beta production through targeting of a protein called beta-secretase. Within the brain, a larger protein (called 'amyloid precursor protein') is cut down into smaller pieces so that it can be cleared out of the brain. Beta-secretase cuts this in a specific place, creating amyloid-beta. This then sometimes sticks together to form amyloid plaques, which leads to Alzheimer's disease.
Another subgroup of flavonoids, the catechin family, was also investigated. This group of chemicals is absorbed easily and also prevents the production of amyloid-beta. In one of the studies, conducted in mice, supplementing the diet with catechin decreased amyloid-beta plawues and amyloid-beta levels. The researchers suggest this this might also be as a result of stopping beta-secretase from working to produce amyloid-beta.
Understanding exactly how these chemicals in food may work is important as it then provides targets for further investigation and treatment development. More research is now needed to see if these changes in levels of amyloid-beta will prevent the development of dementia or improve symptoms in those already with the condition.
What happened next? Future work and additional grants
This work has been exciting as it strengthens the link between diet and a reduced risk of dementia. However, much more research is required to fully understand the precise role flavonoids are playing in Alzheimer's disease.
However, much more evidence does show that diets rich in fruits and vegetables, such as the Mediterranean diet, reduce the risk of developing dementia.
How were people told about the results? Conferences and publications
Williams RJ, Spencer JP. Flavonoids, cognition, and dementia: actions, mechanisms, and potential therapeutic utility for Alzheimer's disease. Free Radic Biol Med. 2012 Jan 1;52(1):35-45. Epub 2011 Sep 17. Review.
Hoey, S.H., Buonocore, F., Cox, C.J., Hammond, V.J., Perkinton, M.S., Williams, R.J., 2013. α-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid receptors couple directly to non-amyloidogenic processing of amyloid precursor protein and suppress synaptic amyloid-beta production. PLoS ONE. Vol 8(10): e78155
Cox CJ, Choudhry F, Peacey E, Perkinton M, Howlett D, Francis PT and Williams RJ. Dietary (-) epicatechin as a potent inhibitor of beta-secretase APP processing. (under review).
University of Bath Research Day, January 2011 Cox C, Wonnacott S and Williams RJ. Development of cell based assays to measure APP processing in primary cortical neurones.
ARUK Research Conference, Leeds, March 2011 C.J. Cox, V.J. Hammond, R.J. Williams – Development of cell-based assays to measure APP processing in neurones: a platform for screening dietary flavonoids.
ARUK Research Conference, Birmingham, March, 2012 C.J. Cox, S. Wonnacott, R.J.Williams – Catechins as novel inhibitors of beta secretase mediated amyloid precursor protein processing.
Society for Neuroscience, New Orleans, September 2012 C.J. Cox, F. Choudhry, D.R. Howlett, P.T. Francis, R.J. Williams - Epicatechin Inhibits Beta-Secretase Mediated APP Processing and Reduces Amyloid Beta Pathology in APP/PS1 Transgenic Mice
Alzheimer's Society Research Conference, Leeds, October 2012 C.J. Cox, F. Choudhry, D.R. Howlett, P.T. Francis, R.J. Williams – Epicatechin Inhibits Beta-Secretase Mediated APP Processing and Reduces Amyloid Beta Pathology in APP/PS1 Transgenic Mice.
Conferences and presentations:
June 2011 – ARUK Network Public Meeting, Bath – Dietary flavonoids and dementia.
October 2011 - Alzheimer's Café, Westbury - Diet and Dementia
March 2012 – Represented the AMRC at the 1st Voice of the Future event at the Houses of Parliament.
July 2014 – Alzheimer's Society Research conference – Dementia Research Leaders showcase