The findings may help to explain why decades of study into the causes of the disease have so far failed to lead to a cure.
Alzheimer's disease is widely believed to be caused by the gradual accumulation in the brain of amyloid-beta peptide which is toxic to nerve cells. Amyloid beta peptide is formed from a protein known as APP, which is found in three forms. Most research into APP - a key area of study for the disease - does not distinguish between the different forms of the protein.
The findings, published in the Journal of Biological Chemistry, show that amyloid beta peptide is actually created mainly by just one form of APP - known as APP695 for the number of its amino acids. APP695 is found at greater concentration in brain and nerve cells, but this study - funded by the Medical Research Council and the Alzheimer's Research Trust - is the first time the significance of that has been shown. This discovery will now enable research to focus more clearly on the exact mechanism by which amyloid beta peptide accumulates in the brain.
"Research into amyloid beta peptide has been going on for more than 20 years and while treatments have made it to clinical trials, nothing has proved truly effective against this disease," says Professor Tony Turner, from Leeds' Faculty of Biological Sciences, who co-led the research. "This could be because research to date has been a bit of a blunt instrument: scientists have essentially been working on too broad a field. Our findings will allow researchers to target their work much more precisely."
The study of APP695 also led the scientists to identify a potential new factor in the development of Alzheimer's. When APP is broken down, it forms another protein called AICD. The researchers discovered that AICD formed from APP695 switches on certain genes within nerve cells that may then damage the cell. The process is unique to nerve cells and AICD formed from the other forms of APP does not have this effect.
"AICD has been detected before, but because studies haven't differentiated between the different forms of APP, there was no consensus on its role," explains co-researcher Professor Nigel Hooper. "It seems likely that AICD formed from APP695 is a contributing factor in the deterioration in nerve and brain cells which leads to Alzheimer's. This provides another avenue for research into a potential cure for the disease."
Professor Chris Kennard, chair of the MRC Neurosciences and Mental Health Board, said: "This is the latest study from a long-term research collaboration to significantly further our understanding of neurodegenerative diseases, such as Alzheimer's Disease. It forms part of a £4.1m investment by the MRC and is a shining example of where fundamental research, which unravels the complex biology of disease, can provide the building blocks for potential treatments in future."
Dr Simon Ridley, Head of Research at the Alzheimer's Research Trust, said: "This study gives us important new insight into the role of APP in Alzheimer's disease, and could have significant implications for future research in this area. We must now build on these findings with more research, as this is the only way we will be able to find an effective treatment for dementia."
Over 820,000 people in the UK live with dementia and one in three over 65s will die with some form of the disease. The Alzheimer's Research Trust estimates that the annual cost to the UK economy is £23 billion.
Graham Askew, Simon Walker, BBSRC (Jan 2018), £699,781
Jennifer Tomlinson, Royal Society (Jan 2018), £512,801
Adrian Whitehouse and colleagues in School of Chemistry and University of Liverpool, MRC (Nov 2017), £622,319
Michelle Peckham, Neil Ransom, MRC (Nov 2017), £495,159
Dave Lewis, British Council India (Nov 2017), £22,540
Elton Zeqiraj, Royal Society (Nov 2017), £15,000
Hannah Dugdale, Royal Society (Nov 2017), £15,000
Shaunna Burke, Cancer Research UK Innovation Grant (Nov 2017), £20,000
Alex O'Neill and colleagues in Chemistry, BBSRC (Nov 2017), £431,865
Jessica Kwok, Wings for Life (Nov 2017), £87,365
Tom Bennett, BBSRC (Oct 2017), £523,679
Neil Ranson, Darren Tomlinson, BBSRC (Oct 2017), £494,318
Nikita Gamper, BBSRC (Oct 2017), £490,426
Amanda Bretman and colleagues from UEA, NERC (Oct 2017), £430,886
Juan Fontana, Rosetrees Trust consumables grant (Oct 2017), £22,500
Helen Miller, DSM Nutritional Products AG (Sep 2017), £69,988
Neil Ranson, Juan Fontana, Mark Harris, Michelle Peckham, Ralf Richter, Peter Stockley, Patricija Van Oosten-Hawle and colleagues in Engineering, FMH and MAPS, Wellcome Trust Equipment Call (Sep 2017), £418,000
Jamie Johnston, Physiological Society (Sep 2017), £10,000
Frank Sobott, Adrian Goldman, Mark Harris, Andrew Macdonald, Stephen Muench, Sheena Radford and colleagues in FMH and MAPS, Wellcome Trust Equipment Call (Aug 2017), £415,000
Ralf Richter, David Brockwell, Eric Hewitt, Jessica Kwok, Emanuele Paci and MAPS/FMH, BBSRC (Jun 2017), £600,000
Eric Blair, Adrian Whitehouse, Nicola Stonehouse, Alison Baker, Richard Bayliss, Joan Boyes, Ryan Seipke, Sally Boxall and MAPS/FMH, BBSRC (Jun 2017), £376,000
Stefan Kepinski, Yoselin Benitez-Alfonso, Tom Bennett, Michelle Peckham, BBSRC (Jun 2017), £331,000
Roman Tuma, Lars Jeuken, Paul Millner, Sheena Radford, Peter Stockley and MAPS/FMH, BBSRC (Jun 2017), £222,000
Vas Ponnambalam, Darren Tomlinson, Stephen Wheatcroft, BHF (May 2017), £107,878
Graham Askew in collaboration with Bangor University, BBSRC (Mar 2017), £477,383
Stephen Muench, BBSRC (Mar 2017), £132,945
Nic Stonehouse, MRC (Mar 2017), £906,341
Bill Kunin, Steve Sait, BBSRC (Mar 2017), £602,831
Adrian Goldman, EU (Mar 2017), £546,576
Sheena Radford, Wellcome Trust (Mar 2017), £1,836,482
Jamie Johnston, Royal Society (Mar 2017), £15,000
Tom Bennett, Royal Society (Mar 2017), £15,000
Beatrice Filippi, Royal Society (Mar 2017), £15,000
Ryan Seipke, BBSRC (Feb 2017), £52,116
Mary O'Connell, BBSRC (Feb 2017), £46,986
Hannah Dugdale, NERC (Feb 2017), £504,138
Anastasia Zhuravleva, EPSRC (Jan 2017), £100,792
Richard Bayliss, Cancer Research UK (Jan 2017), £1,600,000
John Barr, EU (Jan 2017), £339,000
Mark Harris, Royal Society (Jan 2017), £250,000
Alison Dunn, NERC (Jan 2017), £105,000
Alex Breeze, Pancreatic Cancer Research Fund (Jan 2017), £180,000
Alison Dunn, NERC (Dec 2016), £18,000
Lisa Collins, BBSRC (Dec 2016), £1,681,835
Brendan Davies, Leverhulme Trust (Dec 2016), £247,555
Alan Benson, Mark Drinkhill, Ed White, British Heart Foundaion (Dec 2016), £217,223
Adrian Goldman, Royal Society (Dec 2016), £82,999
Lisa Roberts, Alex Breeze, Brendan Davies, Timothy Devinney, Oliver Harlen, Joseph Holden, Anthea Hucklesby, Pamela Jones, Philip Mellor, RCUK (Nov 2016), £484,172
Lisa Roberts, Alex Breeze, Brendan Davies, Timothy Devinney, Oliver Harlen, Joseph Holden, Anthea Hucklesby, Pamela Jones, Philip Mellor, Wellcome Trust (Nov 2016), £119,343
Katie Field, Rank Prize Funds (Nov 2016), £20,000