An international team of researchers has used human data for the first time to quantify the speed of different processes that lead to Alzheimer’s disease and have found that it develops in a very different way than previously thought. Their results could have important implications for the development of possible treatments.
One of the main conclusions of the new work, which is published in the journal Science Reports , reveals that instead of starting from a single point in the brain and initiating a chain reaction that leads to the death of brain cells, the disease of Alzheimer’s reaches different regions of the brain at the same time. The speed with which the disease kills cells in these regions, through the production of clumps of toxic proteins, limits the speed with which the disease progresses overall.
The researchers used post-mortem brain samples from Alzheimer’s patients, as well as PET scans from living patients, ranging from those with mild cognitive impairment to those with advanced Alzheimer’s disease, to track the aggregation of tau, one of the two proteins. key involved in the condition.
In Alzheimer’s disease, tau and another protein called beta-amyloid accumulate in tangles and plaques, collectively known as aggregates, causing brain cells to die and the brain to shrink. This results in memory loss, personality changes, and difficulty performing daily functions.
By combining five different data sets and applying them to the same mathematical model, the researchers observed that the mechanism that controls the rate of progression in Alzheimer’s disease is the replication of aggregates in individual regions of the brain, and not the spread of aggregates from one brain. region to another.
The results open up new ways to understand the progress of Alzheimer’s and other neurodegenerative diseases, and new ways to develop future treatments.
A very difficult disease to study
For many years, the processes within the brain that lead to Alzheimer’s disease have been described using terms such as “cascade” and “chain reaction.” It is a difficult disease to study, as it develops over decades, and a definitive diagnosis can only be made after examining samples of brain tissue after death.
For years, researchers have relied heavily on animal models to study the disease. The results from the mice suggested that Alzheimer’s disease spreads rapidly, as clumps of toxic proteins colonize different parts of the brain.
“Alzheimer’s was thought to develop in a similar way to many cancers: aggregates form in one region and then spread throughout the brain,” explains Georg Meisl of the Cambridge Department of Chemistry Yusuf Hamied, the first author of the paper. “But instead we found that when Alzheimer’s begins, there are already aggregates in multiple regions of the brain, so trying to stop the spread between regions will do little to slow the disease.”
This is the first time human data has been used to track which processes control the development of Alzheimer’s disease over time.
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