Magic number 695 opens up new areas for Alzheimer’s research

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.