An earlier and clearer picture of brain disease

During their lives millions of people suffer from Alzheimer’s, Parkinson’s or other degenerative diseases of the brain. By the time symptoms appear, the disease has progressed for many years. Wallenberg Clinical Scholar Oskar Hansson wants to use new tests to identify diseases earlier and understand them better.

Oskar Hansson

Consultant and Professor of Neurology

Wallenberg Clinical Scholar 2018

Institution:
Lund University

Research field:
Neurodegenerative diseases

Alzheimer’s disease, Parkinson’s, and many other forms of dementia are called neurodegenerative diseases. They break down cells in the brain and destroy memory, cognitive ability and many other neural functions. Over time, sufferers may lose their personality as well as their ability to look after themselves. Some 50 million people across the world are living with various forms of dementia. That figure is expected to triple over the next thirty years.

Dementia was long seen as part of the natural ageing process, but nowadays there is a huge amount of research into potential therapies. Unfortunately, only limited progress has been made.

“There are no cures – nothing that slows down or halts these diseases. All we can do is alleviate the symptoms,” says Oskar Hansson, who is a consultant and professor of neurology at Lund University.

Major clinical trials have been initiated on several occasions, but without success. Hansson pinpoints two main reasons: we still do not know exactly why brain cells die; and to date the drugs have been tested on patients whose conditions are too far advanced.

“For them it’s probably too late – too many neurons have already died. We must intervene at a much earlier stage if we are to halt or reverse the process.”

These diseases have often been studied in animals, and Hansson is convinced that more research on humans will be needed to understand the underlying causes. Fifteen years ago he began to develop tests capable of detecting the disease long before symptoms became apparent. The result is two new methods: measuring substances in cerebrospinal fluid (which surrounds the brain), and brain imaging using PET scanning.

Early and accurate diagnosis means more support

Hansson and his colleagues are measuring two proteins in spinal fluid: beta-amyloid and tau.

“It takes a doctor maybe fifteen minutes to take the sample – it’s not much more trouble than taking a blood sample. It’s taken many years to improve the technique, but it’s starting to become stable enough to be used by health care providers around the world.”

In Alzheimer’s beta-amyloid clumps together to form plaque in the brain, a process than may start ten to twenty years before the patient is diagnosed with the disease. Tau forms aggregations later, perhaps five years before diagnosis. That is the point at which brain cells start to die.

Imaging of b-amyloid and tau proteins using PET scanning has enabled researchers to study the part of the brain where the disease begins in different patients. Thanks to this technique, researchers have been able to see how early beta-amyloid plaque aggregates, and have also seen that beta-amyloid must be present in order for Tau to start aggregating and spreading throughout most of the brain.

PET scanning is also a quick and reliable way of determining whether a patient is in fact suffering from Alzheimer’s.

“Although there is no cure, early diagnosis means the patient can receive drugs to alleviate the symptoms, as well as help and support,” Hansson says.

Accurate diagnoses are also essential for effective drug studies. So far diagnoses have been based solely on symptoms, and research has shown that as recently as ten years ago around 30 percent of patients purportedly suffering from Alzheimer’s had been wrongly diagnosed. This naturally meant there was a risk of testing drugs on the wrong disease.

Research – being involved and making a difference

Hansson will now continue his efforts to identify biomarkers in blood as well. A key aim here is that it should be possible for samples to be taken in primary health care. That is the first stop for most patients suffering from memory impairment.

“I really do hope we’ll be able to improve diagnostics in primary health care. At present, about half of patients with dementia are not correctly diagnosed. Those patients will not be given the drugs that do in fact alleviate the symptoms.”

He is also trying to develop new models to compare cells from people with and without Alzheimer’s, to gain a better understanding of the disease mechanisms.

“It is harder than studying the disease in animal models, but I think it’s necessary. Researchers have so far developed over 300 therapies that work on mice with Alzheimer’s. Not one of them has led to a drug for humans.”

“It’s a great honor to be chosen as a Wallenberg Clinical Scholar. The long-term funding I’m receiving also represents an incredible opportunity. It means we can commit to riskier projects – projects that also offer more potential than those that are a safer bet.”

For Hansson, research is more than just a job – it is an abiding interest. Even as a boy he thought science was exciting. But early on he was most interested in physics.

“I thought it was fun to spend my summers reading about Einstein’s theory of relativity. Perhaps I was a little crazy…”

After just a few semesters of medical studies he began research on the side. Now he works one day a week as a doctor, and devotes the rest of his time to research.

“I need to feel I’m involved, that I’m making a difference, helping to improve things. My research gives me that feeling. But it’s great to combine it with my role as a doctor. It’s rewarding to meet patients, and to be able to help them. And it’s also important for me to understand the problems they experience in their daily lives, and identify topics for research on that basis. Then I can be sure that my research is clinically relevant to many people.”

Text Lisa Kirsebom
Translation Maxwell Arding
Photo Magnus Bergström