What is Alzheimer's?

This week marked the 150^th birthday of Alois Alzheimer - the man who first described the disease he gave his name to over 100 years ago in 1906. The condition is one of a number of disorders that we collectively call dementia. These are progressive diseases that gradually rob sufferers of their mental faculties. They also become more common as we age. In countries like the UK, 1 in 6 people over the age of 80 are affected to some degree. But it also has a very profound effect on the people who care for victims of Alzheimer's.

Susie Hewer is a Guinness World Record holder for her extreme knitting. This year, she crocheted 139-metre long crochet chain while simultaneously running the London marathon. She did this to raise awareness for Alzheimer's after her mum Peggy developed the disease.

Susie - She started to get quite depressed. She was very withdrawn. The next phase was she started to have wandering incidents, because she'd lived with us and my husband worked at home, it hadn't been really a problem until then. But one day, he came downstairs, he found her sitting outside on the stairs because he wondered where she was and she said, "Well, I couldn't get in." he said, "Well, why didn't you ring the doorbell?" And she hadn't thought about that.

The next thing that sort of changed our lives dramatically was, I left her in the library while she chose a book. I went over the road to the cashpoint and came back again  5 minutes later, she wasn't there. So, I looked up and down the road, couldn't see her, went running one way and thankfully, I found her walking really fast with her head down. I said, "Mom, what's going on?" She said, "Well, you moved the car. I didn't know where you were, so I'm heading for home."  She was heading in completely the wrong direction and the car was actually outside. So, at that point, we realised that the wandering could become a problem so I left my job to care for her full time. 

For a while, it was sort of alright because we could go out together and we could go round gardens. Little by little these things disappeared from her and then we started to enter the really unpleasant phase. She didn't sleep at night at all. Then she became doubly incontinent and it's so humiliating for the person, but thankfully, by that stage, she was sort of beyond knowing what was going on.

With us this week to explain more about the causes of Alzheimer's disease and how scientists are trying to develop treatments to halt or reverse the disease are Chris Dobson from the Department of Chemistry at Cambridge University and Jody Mason a Biochemist at Essex University. They spoke to Chris Smith about what's actually going on in the brains of people who have Alzheimer's disease.

Chris D. - The fundamental thing that's happening is that our brain cells, our neurons are becoming damaged and ultimately dying.The result is that we find it more difficult to remember new things. We start as the disease progresses to begin to have difficulty in recalling the things we knew before. Ultimately, as you've heard from Susie's story, you begin to lose a great deal of control of daily activities and ultimately, you don't even recognise your friends and relatives.

Chris - What causes those nerve cells to die?

Chris D. - Well, we now know that it's caused by pathogenic agents. Pathogenic agents in this case are not bacteria or viruses from the outside world. They're actually species which develop from our own molecules particularly proteins. What happens is that these protein molecules and proteins I should say carry out every process that occurs in our body - so breathing, moving, eating, thinking - all are carried out by proteins. We have about 100,000 different proteins and they carry out all these functions because of their intricate structures. The way the one can think about these is proteins are made from series of building blocks called amino acids. The exact order of the building blocks determines which protein you make.  This information is stored in our genomes, in our DNA. So, when proteins are made in the cell, they come out as long thin chains and to function, they have to fold up, into very specific, beautifully intricate structures and then they carry out their functions. But sometimes, these molecules which are packed together very closely in our cells so we can do fast chemistry and pass on messages, start to clump together. They misfold. They lose their correct structures and start to clump together. In the Alzheimer's disease, the primary protein that's involved or a fragment of protein is called the Abeta peptide. When this protein aggregates, it forms the familiar clumps and plaques in the disease. But actually, we now know it is not these plaques and such that cause the damage. It's a smaller aggregate, about the same size as viruses or bacteria that actually interact with the cells and move around and cause the disease to spread. We can understand how the disease kills, how the disease develops through cells dying and how this can then spread to other parts of the brain.

Chris - Jody, that Abeta peptide that Chris is talking about, where does that come from and what is it?

Jody - Well, the a-beta peptide is cut down. It's produced from a much, much bigger protein called the amyloid precursor protein. A couple of enzymes, molecular scissors come along and snip out this small section from the amyloid precursor protein. That produces this very small peptide. It's about 37 to 43 amino acids.  It's that peptide that's incredibly sticky. It self-associates and then it forms into these very toxic amyloid plaques.

Chris - So, cells normally make the beta amyloid precursor protein. It's part of what your cells normally make as part of going about their cellular business in your brain. For some reason, a chunk of it gets chopped off which then is what starts to build up into these aggregates in the brain that ultimately lead to Alzheimer's.

Jody - That's correct and these amyloid plaques are exactly the type of - are exactly the things that Alois Alzheimer would've seen when he was looking down his microscopes 120 years ago.

Chris D - That's a very nice description. The interesting thing is that Alzheimer's is one a number of diseases that include Parkinson's disease, motor neuron disease, and even type 2 diabetes which were associated with these aggregation phenomenon of proteins. What we now know again is that our proteins all have a tendency to aggregate, but there are lots of protective mechanisms that come in. some of them are very motive words like molecular chaperons that look after our proteins and stop them making these improper interactions. But as we get older, these mechanisms start to get less efficient. And so, the molecules start to have a high risk of sticking together and once they stick together, then the process has started and progresses, and that's the onset of disease.

Chris - I was going to ask you about that because we read in the beginning that 1 in 6 people over the age of 80 is affected to some degree. But that means 5 out of 6 people Jody, aren't affected. So, what influences the likelihood of people having this big protein chopped up into these small bad bits of protein that then build up?

Jody - But as far as we know, it's a peptide that's being produced naturally throughout life expressed in all tissues. But for some reason - I mean, age is probably the biggest risk factor of all of course. As you live longer, you accumulate more of this peptide. For people with early onset Alzheimer's disease, they're producing more of this peptide. So, these scissors are coming in and cutting more often or there are mutations within the peptide itself that makes it more sticky, and therefore, more susceptible to aggregate, to stick together into these very toxic plaques. So, it's probably down chaperons not removing the peptide efficiently, but as I said, age is the biggest risk factor. So, as you get older, your risks of contracting Alzheimer's disease increases exponentially.

Chris - Anything else people can do Chris, to minimise their risk because there are some, it might be apocryphal claim that people in India have lower rates of Alzheimer's disease and some have suggested that it could be turmeric in the curry that they're fond of because turmeric is an anti-oxidant and it stops you burning out your brain cells, making these proteins that build up pathologically?

Chris D. - I think that there are a lot of very interesting ideas out there but actually, very few of them have got good statistical evidence. By far, the biggest risk factor as Jody says is age. It's really dramatic. At the age of 65, one or two people in a hundred will have symptoms of Alzheimer's disease. By the time you reach 85, it could be 1 in 3. Again, I think it's just chance that does this largely if you don't have particular genetic mutation.

Chris - And just to be clear, this is the loss of brain cells because these proteins are toxic to the brain cells and kill them off.

Chris D. - Absolutely. Once these aggregates start to accumulate and they could start perhaps 20 years before many of the symptoms begin then they start to kill the cells, and then it becomes a sort of chain reaction, a progressive reaction. But going back to your original comment, in terms of numbers, there are nearly a million people in Britain with Alzheimer's disease. There are over 5 million in the US. Worldwide, it's estimated that there are 40 million. More than half of those are in low and middle income countries. So, it's not just a disease associated with the affluent world because longevity is increasing everywhere. It's predicted in the next 35 or 40 years, that number will increase by at least a factor of 3.