TACKLING DEMENTIA
Dementia, of which Alzheimer’s Disease is the most common form, is a life-changing disease for which there is no cure. Helen Harvey (words) and Andy Jackson (visuals) went to the Centre for Brain Research in Auckland to find out about their world-leading
The human brain arrives in a small white chilly bin.
Its entrance sets off a flurry of activity with 10 scientists involved in preparing ice, tin foil, trays.
Blood vessels are removed as is cerebrospinal fluid – a clear liquid found in the brain and the spinal cord. The brain is cut in half.
Each hemisphere gets cut into
60 blocks according to the functional regions , such as the part that affects speech, movement or memory.
In another part of the lab Dr Brigid Ryan, 31, holds up a vial of blood. She has just taken it from a person whose family has a mutated gene that causes frontotemporal dementia.
As she does genetic studies on the blood and isolates the DNA, Ryan can tell whether the person has the mutation or not.
Across the room Dr Helen Murray, 27, is looking down a microscope at two types of protein – amyloid and tau – that cause problems in the brain of a person with Alzheimer’s disease.
The Centre for Brain Research at Auckland University is on the
5th floor and looks out over the Auckland Domain. It was set up in
2009 by Alzheimers New Zealand patron and one of the world’s leading neuroscientists, Professor Sir Richard Faull.
It started with 25 research groups across the university and now there are 70, Faull says.
‘‘So, it’s grown hugely. That’s about 450 people. That’s marvellous. We try and provide an environment where they collaborate. On this floor there are
10 research groups together. We want to do the best brain research in the world and we are in all sorts of ways. We’re growing human brain cells which is incredible, very few places in the world are doing that.’’
The centre is built around what Faull called three pillars – researchers, medical professionals, and community groups, like Alzheimers New Zealand.
‘‘We have the most special relationship with the families because they give us the brain of their loved one, when they die, for our human brain bank for research studies.’’
Located in the Centre for Brain Research, the Neurological Foundation Douglas Human Brain Bank is funded by the Neurological Foundation. Back in 2006 a woman who had frontotemporal dementia decided to donate her brain to the brain bank.
Four out of her six siblings had the disease, as did her father. Researchers sent some of the brain tissue away to be tested, which confirmed the woman carried a known mutation that causes frontotemporal dementia.
Last year, Ryan, a research fellow who is overseen by Associate Professor Maurice Curtis, set up a research team of 12 to study the family.
The family are interested in being involved, because it is going to affect them down the generations and are very engaged and enthusiastic about the research. ‘‘They see humour in things when people start acting unusually.’’
In the early stages of frontotemporal dementia people lose their inhibitions, because the frontal lobe of the brain is affected, and can make inappropriate comments.
The family are aware they might only have 50 years of health, because that’s when the dementia can start to develop. They often have huge gatherings of all the cousins and there is lots of support, she says.
But, which family members have the gene will remain Ryan’s secret. Ethically, the decision has been made not to reveal the results, she says.
‘‘Because we don’t have the expertise to take people through genetic counselling. It’s a huge burden. If a child wants to find out and finds they have the mutation that indicates the parent definitely has it. And the parent might not want to know.’’
Ryan is interested in genetic diseases and the type of dementia she is interested in has a genetic cause.
The majority of drugs for dementia haven’t worked, she says. ‘‘We think that’s because by the time someone has dementia their brain is so badly damaged that it’s basically too advanced to be able to treat it.’’
So, she is trying to find a way to identify dementia in its earliest stages.
‘‘We are trying to develop a test, so we can say to someone you don’t have dementia now but we can predict that in 20 years time you will have. And we think that is really important because that’s the point we need to be giving people treatments.’’
They think there are changes in the brain decades before the person is at the stage they are diagnosed. So, the researchers are looking for bio-markers, something they can measure, that will show the changes.
The difficulty is how to measure these bio markers in people if it is not known who is going to develop dementia later on, Ryan says.
‘‘The most obvious way to do it is to take measurements in thousands of people when they are 35, follow them up in 50 years and see who has developed dementia and then sort of tracking back. But that takes a lot of time and costs a lot of money to have that many people involved because only a small percentage of them will get dementia.’’
Which is why working with the family is so important and what makes the research so groundbreaking. While scientists around the world do similar research, they work with much smaller groups of people who are not related.
Because the family members who have the mutation will definitely develop dementia in the future, Ryan can look at what is happening in people who are in the really early stage of dementia and the findings from the study might be beneficial for other types of dementia, particularly Alzheimer’s.
The intention is to continue with the study for as many years as they can, but funding is an issue, she says.
Ryan spends half her time in the lab and the other half coordinating the team and applying for funding.
Total research funding for dementia was about $4.8 million in 2016, compared to more than $18 million for cancer. Fulltime researchers need to find funding for their own salaries, but Ryan reckons it’s worth it in the end.
‘‘I’m hoping this project will continue to get funded. This is very exciting research.’’
Across the room in the brain bank the brain is still being processed. One scientist is looking after the olfactory bulbs, which go from the nose into the brain, and blood vessels.
A woman is getting the dry ice ready. It’s the snow dry ice, brain bank deputy director Associate Professor Maurice Curtis says.
‘‘It’s so you get a very even freeze. Marika has prepared the trays that go in the freezer and lots of tin foil. It’s much like if you leave the peas in the bottom of the freezer you end up with them getting crusty, this stops the same thing happening to the brain tissue.’’
A researcher takes something out of the freezer – set at minus 80 degrees Celsius; the home freezer is minus 20 – and even with gloves can only hold it for a few seconds.
The small narrow room is bustling with activity and will continue to be like that for the next couple of hours.
The bank contains about 650 whole brains. About 250 of the brains would have come from someone who died of something other than a neurological disease. The rest have Huntington’s Disease, Parkinson’s Disease, Alzheimer’s or other neurological diseases, Curtis says.
‘‘We are able to look at the same area from many different brains to compare normal and Alzheimer’s, normal and Parkinson’s disease and so on.’’
The brain bank sets New Zealand apart in the area of brain research, because banks of human brains are not common and are usually a lot smaller.
‘‘And something else that sets our brain bank apart is we’re able to culture brain cells from the tissue.’’
This means drugs can be tested on brain cells from someone who had the brain disease as opposed to using rodent cells, he says.
The brain bank is governed by the Human Tissue Act and has to abide by its rules. And every three years they have to get their ethics approval renewed.
‘‘The Ethics Committee looks at our processes, how we interact with families, what sort of paperwork we get them to sign, make sure we are telling the family what will happen with the brain tissue and what we are doing with it.’’
They often get calls from people who want to donate their brain, he says. ‘‘We’re certainly interested if people are keen to donate. Then when they pass away we get a call from the family and we can organise with the local mortuary to do the brain removal and they air freight it to us in Auckland where we can process it for future research studies.’’
The hardest place to get brains from is the East Coast, because the closest mortuary is Wellington or Palmerston North. Curtis was a radiographer and loved it, but then he did a paper in neuroscience, which was compulsory, and loved that even more.
‘‘I was so fascinated by the type of things we didn’t know really. The amazingness of the brain. The fact it controls who we are, how we think, how we move, why we care about one thing and the next person couldn’t care less. All that sort of thing is wrapped up in our brain.’’
So, to learn more he did a Master’s Degree, which left him an underqualified scientist and an overqualified radiographer, he jokes.
‘‘I also like taking my work home with me. I like thinking about work outside work and with radiography you don’t live and breathe it. You do your shift and you can’t take your work home. I really wanted a job that was allencompassing, I suppose. I probably now wish the opposite – I’d just like to leave work and go home at five – nah, it’s really good.’’
Dementia is not expected to go away, Curtis says. In fact it’s expected to increase.
‘‘Whether or not scientists and researchers will be able to cure Alzheimer’s disease I’m not sure. But you don’t lie awake dreaming about just making it five per cent better.’’
One of the key areas they’ve been focussing on is the very earliest signs of dementia. They’re interested in olfactory bulbs, where scientists believe the disease starts. Olfactory bulbs are tiny. There is a passage between little fibres that come out of these wee bulbs into the nose to sense smell.
Curtis oversees the researchers and this is something postdoctoral fellow Helen Murray, is working on.‘‘And when you see them
Murray has just published a paper on brain plasticity, which is the ability of the human brain to adapt and change. She was looking at two proteins – amyloid, which clumps together outside the brain cells, and tau, which clumps inside the brain cells. together you have Alzheimer’s disease. In normal ageing you get a fair amount of this happening, but not as heavily as in Alzheimer’s. Especially the tau, which we think is the bad one. If you have a brain cell that is full of clumpy aggregate it’s not going to function as well as it could.’’
Her research looked at how the brain adapts to the tau and amyloid in order to keep functioning.
‘‘All this is happening to the brain up to 10 years before symptoms occur. I think it is amazing the brain can still function with all this bad aggregation going on inside and outside the cells.’’
These tau and amyloid clumps form in the olfactory bulbs very early, Murray says.
‘‘People with Alzheimer’s lose their sense of smell up to 10 years before other symptoms occur.’’
In her new research Murray will be looking at what’s changing, can you delay it and can the brain repair itself and slow the disease down? And how changes that occur in Alzheimer’s disease may begin in the olfactory bulbs and move further into the brain.
‘‘If we could delay the onset of Alzheimer’s by five years you could prevent up to 50 per cent of cases, because people would age more healthily and die of something else.’’