Using a powerful laser imaging technique, a study led by the University of Cambridge in the UK shows how tiny pieces of a protein linked with Alzheimer’s Disease could be the start of a process that leads to the onset and spread of the disease.
The researchers also cautiously suggest the finding offers a plausible explanation as to why head injuries are linked to Alzheimer’s.
For their study, the researchers used a model cell culture, which shows how the disease may take root and develop in the brain.
But they emphasize the limitations of such an approach and warn that the reality is likely far more complicated. Their findings should be treated as just a piece of the puzzle, as lead investigator Clemens Kaminski, professor of chemical physics at the University of Cambridge, explains:
“These are molecular-level glimpses of what may be going on. We are just beginning to see the molecular steps that may provide an explanation for what we see in the brains of patients who have died of Alzheimer’s.”
Prof. Kaminski and colleagues report their findings in a recent online issue of the Journal Of Biological Chemistry.
Their study focuses on a protein called tau, which is normally found in healthy cells. But in brains of people who have died of Alzheimer’s, there are clumps of abnormal tau, which are thought to play a key role in stopping brain cells from functioning.
For their study, they used what they describe as a model culture, which contains cells that behave like neurons and whose basic chemical processes can be observed with laser-based imaging techniques.
They added small amounts of tau to the outside of these cells and were surprised to find they immediately started ingesting the protein.
The uptake of the protein – a mechanism known as endocytosis – appeared also to trigger the process through which the protein begins to form clumps. This led to a chain reaction that affected the “healthy” tau already in the cells – they too started to form clumps.
The researchers say while the model they used has limitations and is likely to be much simpler than real life, they think it offers a plausible explanation about how Alzheimer’s begins.
If true, then the implication is: anything that causes tau to escape from inside cells to the outside could be a trigger – head injuries being a prime candidate.
There are also other possible ways that tau can escape from inside brain cells, and these could be linked to other neurodegenerative diseases, such as brain cancer and Parkinson’s.
The team plans to take their investigations further and identify, for example, how and where a molecule of tau entering a brain cell meets the tau already inside it, and how this leads to clusters of tau. This could reveal targets for treatment.
Most research into treatments for Alzheimer’s and other diseases involving tau clumps have focused on how to remove the clumps once they have formed. This study suggests that finding ways to stop them forming in the first place might be just as important.
Dr. Simon Ridley, head of research at Alzheimer’s Research UK, says:
“Investigating how the tau protein spreads between nerve cells can help researchers better understand what causes the disease and offer new approaches for treatments. It is unclear from this study whether head injury could trigger this molecular process, but it is a risk factor for dementia that needs to be investigated further.”
Funds from the Wellcome Trust, the Medical Research Council and Alzheimer’s Research UK helped finance the study.
In September 2012, a study published in the journal Neurology suggested that professional football players are much more likely to die from Alzheimer’s disease and ALS (Lou Gehrig’s disease).
In that study, researchers from the National Institute for Occupational Safety and Health in Cincinnati, OH, found that professional football players had triple the risk of death caused by diseases that destroy or damage brain cells, compared with other people.