Dementia: I have a 50:50 chance. But I try not to worry

Peter Popham meets the remarkable family from Nottingham who changed the way scientists thought about Alzheimer’s - and offered hope to millions

Suddenly, Alzheimer’s Disease is the new frontier. Like cancer and HIV/Aids when they were thrust into the public consciousness, it presents a massive research challenge. At present there is no treatment for it: some drugs slow its progress, but there are no cures and no way of preventing it. Once the symptoms appear, it is like a cancer that has already metastasised, and by then it is too late – the brain has already suffered irreversible damage. So how can victims be identified before symptoms appear?

One answer is that some forms of Alzheimer’s are inherited, and by testing members of families in which it has been passed down from generation to generation, and identifying what distinguishes those who get the disease from those who do not, researchers can close in on the causes.

Meet Carol Jennings.

In the late 1980s, a team of neurologists at St Mary’s Hospital in west London was hunting the gene which caused familial Alzheimer’s when a letter arrived from a teacher in Nottingham. The decision of Carol Jennings to contact them about her family’s tragic history was to momentously advance our understanding of how and why Alzheimer’s strikes.

Ms Jennings has vivid memories of her father Walter in his prime: the way he sang all the time, his attention to detail, his cheeriness. “He was always really chatty,” she said. “He’d come in and talk to anybody.”

Walter had been in the Navy in the war and those early habits stuck: he would polish his shoes till they shone like a mirror. The eldest of 15 children in a hard-pressed working-class home, he recalled “topping and tailing” with his brothers because of the shortage of beds, and went out to work as a milk boy at 14 to keep the family from going hungry. She remembered the meticulous way he did his job, collecting monthly dues from members of the Nottingham Co-op.

But then in his late 50s things started to go wrong. “Mum was finding that he was doing things that were out of character,” Ms Jennings recalls. “It wasn’t him all of a sudden.” She found he was no longer keeping his account books with his usual care. “Mum would look at his books and found he wasn’t writing things down, he wasn’t doing things right. And that was how it started.

“He was always the life and soul of the party. But all of a sudden he was a different person. If he went in a shop with her he’d wander down the wrong aisle, pick up the wrong things and put them in the trolley or in somebody else’s trolley, he didn’t know what he was doing half the time...”

It didn’t stop there. As the years went by, word arrived that more members of her father’s family were behaving similarly as they approached 60. “Gradually it was going through the family,” she says. “It seemed like each year another one would have developed it. They would ask you something and five minutes later they were asking you the same question.

“I was thinking, what’s going on here? There’s this one, and this one and this one – and I thought, somebody ought to know about this.”

So in 1987 she decided to act. Her GP had told her about the team at St Mary’s Hospital that was researching the causes of Alzheimer’s. Already they had started canvassing for families with the disease through the networks of the Alzheimer’s Society. And one day she took out a sheet of Basildon Bond and wrote down her family tree, indicating those who had the disease and those who didn’t.

At the time Carol’s letter arrived, “Dementia was a real Cinderella subject,” says Martin Rossor, today a senior academic at University College London. “It was thought to be bizarre to go into it.” It was as far back as 1901 that a German psychiatrist called Alois Alzheimer first identified the disease that bears his name. When his patient died and her brain was examined, it was found to be shrivelled and dotted with particles. Those particles, researchers subsequently discovered, were deposits of a protein fragment called beta amyloid, the accumulation of which creates the toxic environment in which the degeneration of the brain begins.

But what caused this cognitive disaster? Scientists believed it was a particular genetic mutation, but nobody had a clue which gene was responsible. “Hunting disease genes,” comments Rossor, “was like looking for a needle in a haystack.” Underfunded and out of fashion, Alzheimer’s research was struggling to make progress until the arrival of Carol’s letter.

When Carol learned that the St Mary’s researchers wanted to know more, she persuaded her relatives to co-operate. “The doctors were fascinated, they came over and everyone in the family took the blood test. They went to every family member and asked questions.”

Rossor comments now: “Carol was very perceptive in seeing the importance of her relatives for research.” As this variant of the disease was inherited, with every child having a 50:50 chance of succumbing to it, by screening all family members the researchers could log the genetic differences between those with the disease and those without it. The team was able to establish beyond doubt that the family’s disease was caused by a mutated gene on chromosome 21 – “the same gene,” Rossor point out, “that codes for the amyloid protein that was observed by Alzheimer.” Those with the gene got the disease; those without it did not. There was no room for doubt.

The discovery was made in 1991 by a young researcher called Alison Goate. The clarity and certainty were exciting. Goate, now a professor at Washington University, recently told the New York Times: “Sometimes in science you generate the data gradually. But this was like, boom, a eureka moment.” She remembered thinking, “I am the first person to see a cause of Alzheimer’s disease.”

It was only the start of Ms Jenning’s family’s contribution to science. The new knowledge gave researchers the incentive to develop drugs aimed either at stopping the plaques from developing, or clearing them away once they were found.

Two problems beset Alzheimer’s research. One, as Martin Rossor points out, is that “the brain is an inaccessible organ – you can’t go in there and start taking things out.” The other is that, even before the earliest symptoms appear, irreversible damage has been done. “The brain begins to shrink before symptoms appear,” says Rossor. Hence the huge value of a family such as Ms Jennings’s whose younger members can be studied decades before anything appears to be wrong. “How does the disease start, and how do you measure its progress? These were the questions we were asking,” says Rossor, “and Carol’s family have made a profoundly useful contribution to our knowledge. It’s before problems appear that you have the chance to make an intervention to slow or cure it.”

As the only disease among the 10 deadliest that cannot be prevented or cured, fighting it has, belatedly, become an international priority. The work on Carol’s family was the forerunner to the biggest research effort into familial Alzheimer’s ever undertaken. Called DIAN, for “Dominantly Inherited Alzheimer Network”, it involves 10 times as many people as in the original British study, as well as families in the US, Australia, Germany and Spain.

Will it produce a cure? Rossor is cautious. “There aren’t many cures in medicine,” he says, “but amelioration can be dramatic. Recovery of the brain’s deficit in patients who already have symptoms may not happen, but by getting in at a very early stage of the disease we may be able to delay its onset and progression.”

Meanwhile, Carol and her family must deal with the frightening fact that half of them will develop the disease. Carol is now 58, the same age as her father when he first started making mistakes in his accounts, but she is not tempted by the idea of learning whether she too carries the mutated gene on chromosome 21.

To have the test, you’ve got to actually go to them and say, I want to know,” she points out. “And I never did want to know. Having the test has always been an option: I could find out now. But I think I would just collapse in a heap if I thought, ‘This was it’.”

In Part 3 Tomorrow: David Blunkett - 'Why I'm giving my brain to science'