Although it’s been a scientific mystery for decades, it’s now been linked to “necroptosis” – a form of cellular suicide, which scientists are calling said findings an “exciting” development.
What does it all mean?
According to Alzheimers.co.uk, amyloid is “a protein that is found in our brains and bodies, but in Alzheimer’s disease, amyloid sticks together and forms different sized clumps that later become plaques in the brain.”
Tau is a microtubule‐associated protein that “forms insoluble filaments that accumulate as neurofibrillary tangles in Alzheimer’s disease and related tauopathies,” the National Library of Medicine states.
“Under physiological conditions, tau regulates the assembly and maintenance of the structural stability of microtubules. In the diseased brain, however, tau becomes abnormally hyperphosphorylated, which ultimately causes the microtubules to disassemble, and the free tau molecules aggregate into paired helical filaments.”
But even with all this knowledge, scientists still couldn’t figure out why – until now, it seems.
So… what did they find?
Researchers are now saying the abnormal amyloid starts to build up in the spaces between the neurons, leading to brain inflammation (which neurons dislike), resulting in a change to their internal chemistry.
Tangles of tau appear, and the brain cells start producing a specific molecule called MEG3, which triggers death by necroptosis. However, it’s been found that the brain cells survived once the researchers found a way to block MEG3.
“This is a very important and interesting finding,” researcher Prof Bart De Strooper said. “For the first time, we get a clue to how and why neurons die in Alzheimer’s disease. There’s been a lot of speculation for 30-40 years, but nobody has been able to pinpoint the mechanisms.”
They were able to figure this out after human brain cells had been transplanted into the brains of genetically modified mice. The animals were programmed to produce large quantities of abnormal amyloid.
The discovery that blocking the MEG3 molecule could prevent brain cell death could lead to a “whole new line of drug development”.
Dr Susan Kohlhaas, from Alzheimer’s Research UK, said the findings were “exciting”, even though still being at such an early stage.
“This discovery is important because it points to new mechanisms of cell death in Alzheimer’s disease that we didn’t previously understand and could pave the way for new treatments to slow, or even stop disease progression in the future,” she added.