An increasing burden on public health across the globe, Alzheimer’s is an intensely studied disease and promising research often hits the headlines. Just the other day, for instance, a study published in the prestigious journal PNAS kicked up a storm in the media because of the potential implications of the results: that Alzheimer’s could be reversed.
One of Walacea’s successful crowdfunding campaigns is an Alzheimer’s project, and interestingly there are some links between this research and the recently published study. We therefore decided to catch up with the scientist behind the former, postdoctoral researcher Dr Eloise Mikkonen, to chat about both pieces of research and what we could learn from them, and whether the hype is justified.
But first things first, what did the new study find? Researchers from Hong Kong and Glasgow universities managed to reverse the memory problems of mice with Alzheimer’s-like disease, in addition to reducing the build-up of toxic clumps of protein, called beta-amyloid plaques, which are characteristic of the condition.
They achieved this by giving them injections of a molecule called IL-33, a signalling protein produced naturally by the body which plays various important roles in mediating immune system responses. The rationale for testing this out as a potential treatment stems from the fact that the brains of people with Alzheimer’s commonly show lower than normal levels of IL-33, and several different mutations in the gene that makes IL-33 have been linked with Alzheimer’s.
The team thinks that the injections changed the activity of a type of immune cell called microglia, which are the brain and spinal cord’s primary defence system, boosting their ability to gobble up beta-amyloid and putting them in anti-inflammation mode. That’s an important find, as work by Mikkonen and others has found that inflammation plays a role in the progression of Alzheimer’s, something that she intends to scrutinize further in her crowdfunded research.
But as is often the case with science, things aren’t quite as black and white as they may first seem. As Mikkonen explains: “Genetic investigations of Alzheimer’s disease have revealed that inflammation plays a role, but it isn’t clear as to how. It could be that some inflammatory factors decrease and others increase, and there needs to be a certain pattern which leads to Alzheimer’s disease.
“It should be noted that some inflammatory factors are beneficial in certain diseases, whilst being detrimental in others… all in the same body at the same time!”
Mikkonen also points out that mice don’t naturally produce the proteins which result in the characteristic brain lesions seen in Alzheimer’s, so the animals have to be mutated for this kind of study. We should therefore be cautious about jumping to conclusions in humans, a message that the researchers have actually been quite clear about. That said, animals models are incredibly useful tools in medical research, so we shouldn’t dismiss this as irrelevant.
Another important issue Mikkonen raises is that removing the beta-amyloid plaques could actually release toxic molecules into the brain, and therapies that have attempted to do this before have failed. In addition, her work has shown that these plaques are surprisingly common in non-demented individuals.
“Does this mean that if they lived long enough, they would eventually develop Alzheimer’s?” Mikkonen ponders. “Or do they have some additional protective factor that we don’t know about that differs from those that succumb to the disease?”
These are questions that she seeks to address in her research, which will involve analysing one of the biggest brain samples in the world, totalling more than 1,300 people. Fewer than 30 of these individuals had memory problems or early stages of dementia, so Mikkonen will look for the presence or absence of brain lesions linked with Alzheimer’s and attempt to identify certain genetic factors or lifestyle choices which could influence the risk of developing them.
So far, the campaign has exceeded its fundraising goal by more than £1,000. As a result, she has introduced stretch goals which, if met, will allow further rounds of data analysis to look for potential links between disease progression and various factors, like exercise and blood type. Each set of analysis costs £1,000, so do something amazing and dig deep for this brilliant cause!