Alzheimer's discovery 'could help drug research'
5th July 2017 – There is currently no cure for Alzheimer's disease but scientists say they have made a key discovery that could hasten the development of drugs to halt its progress.
A team from the Medical Research Council Laboratory of Molecular Biology in Cambridge say they have, for the first time, charted the inner workings of one of the two types of the abnormal filaments that are found in people with Alzheimer's disease.
Plaques and tangles
In Alzheimer's disease an abnormal protein surrounds brain cells and another protein damages them from within.
The first protein, called amyloid-beta, clumps into plaques which go on to accumulate all over the brain. The other protein, called tau, degenerates and creates neurofibrillary tangles – twisted masses of protein fibres inside brain cells.
Over time, chemical connections between brain cells are disrupted and cells begin to die.
Almost 30 years ago, scientists at the Laboratory of Molecular Biology identified tau protein as an integral component of the lesions found in the brains of people with Alzheimer's and other neurodegenerative diseases.
However, progress in understanding the role of tau has been hampered by difficulties imaging it in sufficient resolution to see its atomic structure.
Seeing the atomic structure
In the latest development, scientists extracted tau filaments from the brain of a patient who had died with Alzheimer's.
Then they inspected the filaments using a technique known as cryo-electron microscopy in which a sample is examined at extremely low temperatures. This allowed them to study the filaments in their natural state without the risk of damaging their structure by preparing them first.
Using specially developed software, they were able to calculate the structure of the tangled filaments in enough detail to model the arrangement of atoms inside.
The study, published in the journal Nature, says that knowing which parts of tau are important for the formation of filaments may be key to developing drugs to treat Alzheimer's.
Finding the lock
Commenting on the findings, Dr James Pickett, head of research at the Alzheimer's Society, says: "Many drugs work like a key in a lock, and this discovery shows us the inner workings of the tau protein 'lock'."
He adds in a statement: "The ability to picture what the lock looks like could help scientists design more precise drugs that act on the tau protein and stop damage to the brain.
"With this knowledge, computer models can measure millions of potential drug molecules against the tau protein, giving immediate clues to suggest which should be tested further."
Dr Pickett says the greater understanding of tau protein could also help the third of people with dementia who have a disease other than Alzheimer's.
"This study could take us into a new era of drug design, but it can take 10-15 years to develop new drugs from this very early stage of drug discovery," he says. "There is currently no cure, but studies like this give us hope that research will deliver better treatments for people with Alzheimer's disease."
Dr Rob Buckle, chief science officer at the Medical Research Council, which helped fund the study, says: "This research opens up new possibilities to study a range of other diseases where the accumulation of abnormal protein filaments plays a role, including Parkinson's disease, motor neuron disease and prion diseases."