An estimated 44 million people throughout the world live with Alzheimer’s. The devastating disease has no cure. However, new research has found that the disease progresses differently than was thought, which could provide some clues on future treatment.
A team led by researchers from the University of Cambridge says that scientists had always thought Alzheimer’s progressed through a “chain reaction,” after tau and amyloid-beta proteins built up in one area of the brain and then spread to another. Instead, they say these protein clusters – known as aggregates – pop up early in different regions of the brain, and their replication in these separate areas leads to progression. Their findings can be read in the journal Science Advances.
The study’s first author Dr. Georg Meisl, from Cambridge’s Yusuf Hamied Department of Chemistry, explains, “The thinking had been that Alzheimer’s develops in a way that’s similar to many cancers: the aggregates form in one region and then spread through the brain. But instead, we found that when Alzheimer’s starts there are already aggregates in multiple regions of the brain, and so trying to stop the spread between regions will do little to slow the disease.”
The researchers conducted their study by looking at brain samples from deceased Alzheimer’s patients and PET scans from living ones. They focused their work on the accumulation of tau protein and used five separate datasets with the same mathematical model. That’s how they discovered that progression was linked to how quickly aggregates caused cell death in individual regions of the brain.
The researchers note that animal models have largely been used to investigate Alzheimer’s, and mouse models had shown that the disease seemed to progress quickly as protein clusters spread to different parts of the brain. That’s where the benefit of using data from humans came in.
Tuomas Knowles, co-senior author and professor from Cambridge’s Department of Chemistry, says, “This research shows the value of working with human data instead of imperfect animal models. It’s exciting to see the progress in this field – fifteen years ago, the basic molecular mechanisms were determined for simple systems in a test tube by us and others; but now we’re able to study this process at the molecular level in real patients, which is an important step to one day developing treatments.”
The team notes that the replication of tau aggregates is slow, taking up to five years. They say this is because neurons are good at stopping their formation. However, treatment may lie in helping neurons become even better at stopping it. They say that knowing replication needs to be targeted is very helpful in determining how to go forward, as well.
The team also hopes to further investigate earlier stages of Alzheimer’s development, which may in turn help with other forms of dementia, traumatic brain injury, and progressive supranuclear palsy, which also involve tau aggregates.