A catalytic trigger has been identified by researchers as a factor in the origin of Alzheimer’s disease. This occurs when the basic make-up of a protein molecule alters, causing a chain reaction and resulting in the demise of neurons in the brain.

Scientists at the Cambridge Department of Chemistry have been able to meticulously chart the pathway that produces unusual forms of proteins which are the core of neurodegenerative illnesses like Alzheimer’s. This leap forward is believed to be an important step nearer to having the capability of diagnosing neurological disorders early and generating new targeted drugs. The analysis is regarded as a milestone in the long-term research by Professor Christopher Dobson and his colleagues in Cambridge. The research is bound to play a pivotal role in the development of drug and diagnostic procedures for dementia-related illness. At the moment there is only limited treatment for symptoms. 

The Alzheimer’s Research Trust revealed in 2010 that dementia costs the UK economy over £23 billion, greater than cancer and heart disease combined. Scientists and clinicians have been urged by PM David Cameron to work together to “improve treatments and find scientific breakthroughs” to deal with “one of the biggest social and healthcare challenges we face”. Alzheimer’s is activated when the normal structures of protein molecules within cells become adulterated. Chemical building blocks known as amino acids are joined together in an order encoded DNA by protein molecules that are produced in cellular ‘assembly lines’. In order to perform their biological activity, new proteins need to be folded into compact and complicated structures. But proteins can ‘misfold’ and catch surrounding normal proteins, which then coil and adhere together in clusters to form masses of defective molecules that mould themselves into awkward protein filaments. Named ‘amyloid fibrils’, these unusual filaments radiate outwards around the place where the focal point or ‘nucleation’ of these irregular “species” materialises. They can form huge deposits of protein or plaque, which has been seen in the brains of Alzheimer’s victims and was once deemed to be the origin of the disease. This was before “toxic oligomers” were uncovered by Dobson and others roughly ten years ago. 

Most of the latest work has been done by researcher Samuel Cohen and others and reveals that when a tiny but crucial stage of defective protein clusters has taken shape, an out of control chain reaction is activated. This exponentially increases the   amount of these protein mixtures and by means of ‘nucleation’, initiates new areas of focus. It is this secondary nucleation method that produces young filaments, consisting at first of clusters that contain only a few protein molecules. These small and widespread ‘toxic oligomers’ lurch precariously around the brain cells and destroy neurons, which eventually leads to memory loss and other symptoms of dementia. The latest research follows close behind that of another pioneering investigation. In partnership with colleagues in London and at MIT, the Cambridge group found a solution to the first atomic structure of one of the harmful amyloid fibril protein filaments. The progress that has been made in research techniques over many years has proved to be fruitful and a solution to the perplexity of these neurodegenerative diseases is beginning to become reality.