Scientists Discover Causes of Alzheimer’s Progression in the Brain

Groups of toxic proteins believed to be responsible for the cognitive decline associated with Alzheimer’s reach different regions of the brain early and accumulate over decades, according to a new study published on Friday (29).

The research, presented in the journal Science Advances, is the first to use human data to quantify the speed of molecular processes in this neurodegenerative disease and, eventually, could have important implications for treatment planning.

It also alters the theory that clumps form in one place in the brain when a chain reaction occurs in other areas — a pattern seen in rats. This dissemination can happen, but it is not the main motivator, according to the researchers.

“Two things made this work possible,” Georg Meisl, a Cambridge University chemist and lead author of the paper, told AFP.

“One was very detailed PET (Positron Emission Tomography) data and various datasets that we’ve gathered, and the other is mathematical models that we’ve developed over the past ten years.”

The researchers used about 400 post-mortem brain samples from Alzheimer’s patients, as well as 100 PET scans from people living with the disease, to track the accumulation of tau, one of the two key proteins involved in the disease.

In Alzheimer’s disease, tau and another protein called beta amyloid build up in nodes and plaques — both known as aggregates — that kill brain cells and shrink the brain.

This, in turn, results in memory loss, personality changes, and inability to perform everyday functions. An estimated 44 million people suffer from the disease worldwide.

exponential growth

Previous research, conducted primarily on animals, has suggested that aggregates form in one region and then spread throughout the brain in the same way that cancer spreads.

The new study points out that while this spread may occur, it is not in fact the main factor in the progression of the disease.

“Once we have these seeds, little bits of aggregate all over the brain, they just multiply and this process controls the speed,” Meisl explained.

The study was able to determine that households take about five years to double in quantity. That number is “encouraging,” according to Meisl, because it shows that the brain’s own neurons are good at neutralizing them.

“Maybe if we can improve it a little, we can significantly delay the onset of serious illness.”

The degree of Alzheimer’s disease is measured according to the so-called “Braak Scale”. The team found that it takes about 35 years to progress from stage three, when mild symptoms begin to appear, to stage six, the most advanced.

If aggregates double in approximately five years, in 35 years they would have multiplied by 128. This exponential growth “explains why the disease takes so long to develop and then the person deteriorates rapidly.”

Using the same method, the team is trying to investigate frontotemporal dementia and traumatic brain injuries.

“Tau is a protein to blame for many types of dementia and it would make sense to explore how it spreads in diseases such as frontotemporal dementia,” said Sara Imarisio of Alzheimer’s Research UK.

“We hope this and similar studies will help develop future treatments that target tau so they have a better chance of slowing down the disease process and benefiting people with dementia.”