Scientists say that they have discovered a possible explanation for how Alzheimer’s disease spreads in the brain.
Alzheimer’s is linked to a buildup of protein plaques and tangles that spread across particular tissues in the brain as the disease progresses. But while the pattern of this spread is well-known, the reason behind the pattern is not.
Now scientists say they have uncovered a potential explanation as to why certain tissues of the brain are more vulnerable to Alzheimer’s disease.
The vulnerability appears to be linked to variations in the levels of proteins in the brain that protect against the clumping of other proteins - variations that are present decades before the onset of the disease.
“Our results indicate that within healthy brains a tell-tale pattern of protein levels predicts the progression of Alzheimer’s disease through the brain [in those that are affected by the disease],” said Rosie Freer, a PhD student at the University of Cambridge and first author of the study.
The results could open up the possibility of identifying individuals who are at risk of developing Alzheimer’s long before symptoms appear, as well as offering new insights to those attempting to tackle the disease.
Charbel Moussa, director of the Laboratory for Dementia and Parkinsonism at Georgetown University Medical Center said that he agreed with the conclusions of the study. “It is probably true that in cases of diseases like Alzheimer’s and Parkinson’s we may have deficiencies in quality control mechanisms like cleaning out bad proteins that collect in the brain cells,” he said, although he warned that using such findings to predict those more at risk of such disease is likely to be difficult.
But others are less convinced by the results. “This might be part of the explanation as to why Alzheimer’s disease kills some cells and not others, but it is undoubtedly a complex problem and this is only part of the answer to that problem,” said John Hardy, professor of neuroscience at University College London. “This paper has only looked at a few brain regions and really only at a few cell [types],” he added. “So it points towards the idea that there is an intrinsic reason for selectivity but it does not really prove it.”
Published in the journal Science Advances by scientists from the University of Cambridge, the research involved the analysis of data relating to more than 500 brain tissues from six healthy individuals, aged between 24 and 57 years of age.
The team looked at the levels of a family of molecules known as mRNA, that are encoded by genes and which are required to produce proteins. From this analysis, the researchers found that they were able to predict the levels of proteins across the brain, allowing them to map the levels of proteins associated with Alzheimer’s disease.
The scientists found that regions of the brain with higher levels of proteins prone to clumping in plaques and tangles corresponded to regions that generally show early evidence of Alzheimer’s disease.
The team also found a link between the susceptibility of regions to Alzheimer’s disease and levels of a group of proteins that are known to affect the clumping of those that form plaques and tangles.
The scientists found that the “vulnerability map”, produced by looking at the levels of these proteins in the brains of healthy individuals, is consistent with the map of how Alzheimer’s progresses.
That, the researchers say, suggests that the vulnerability of particular tissues to Alzheimer’s disease could, in part, be down to a combination of higher levels of plaque and tangle-forming proteins and problematic levels of proteins that affect their clumping.
The scientists say the findings could lead to new ways to predict an individual’s risk of developing Alzheimer’s disease.
“Although we all have these patterns, in some people the patterns are more extreme, and in some others are less. Those in which the imbalance is greater, are more at risk,” said Michele Vendruscolo, co-author of the research, although he stresses that research to back up the suggestion has yet to be carried out.
Dr David Reynolds, chief scientific officer at Alzheimer’s Research UK, said: “These findings suggest that our susceptibility to Alzheimer’s may not only be dictated by abnormal changes in the brain, but by how our brains are hardwired to react to those changes.”
“Understanding the molecular mechanisms that underpin susceptibility to diseases like Alzheimer’s has the potential to open the door to new treatment and prevention approaches,” he added. “Building a complete picture of the biology driving a complex disease like Alzheimer’s gives scientists the best chance of developing effective treatments against it.”