A Trinity College research team has developed a powerful new indicator of developing Alzheimer's disease. The test is highly accurate but more importantly, it warns of the disease long before a patient begins to show signs of the condition.
"Alzheimer's is now the fourth largest cause of death and by 2040 it will become the leading cause worldwide, ahead of heart disease, cancer and stroke," states Prof Harald-Jürgen Hampel, Trinity's professor of psychiatry and principal investigator in its Institute of Neuroscience.
There are now 38,000 patients with the disease here, involving annual treatment costs of €474 million. "In the next 30 years we will see an increase to about 100,000 patients," says Prof Hampel, who also holds the chair of psychiatry at the Adelaide and Meath Hospital, incorporating the National Children's Hospital at Tallaght.
One of the great challenges in tackling the disease is achieving early and accurate diagnosis of Alzheimer's disease. It causes very specific changes in the structure of the brain, the so-called protein "tangles" that appear as the brain tissues degrade and cognitive function slowly and irreversibly declines.
These begin to occur very early on, long before a patient begins to show symptoms, Prof Hampel says. This in turn delays the administration of the drugs now being developed by the pharmaceutical companies. "In order to bring these drugs to the patient you have to detect the disease early. Currently we deliver the drugs too late," he says.
His research group, which is funded by the Health Research Board, Science Foundation Ireland and bodies such as the Alzheimer's Association of the US, focuses on delivering an earlier diagnosis of the disease. "We use high-resolution neuro-imaging at the Trinity College Institute of Neurology (TCIN) and we also study protein markers that give an indication of the disease."
However, Alzheimer's represents a particular challenge. "The disease is a highly complex multifactorial disorder. We think it is going on in the brain for 30 or 40 years before symptoms begin to occur."
Prof Hampel's research team managed to track down a promising protein candidate for the disease known as p-tau 231 (phosphorylated-tau 231). "It is a protein you detect in cerebrospinal fluid. It is a marker of a central disease mechanism and it seems to be entirely associated with Alzheimer's and not with other neurological diseases," he says.
"The p-tau is a specific reflection of the amount of altered cells you have in the brain. The new discovery is the marker p-tau 231 and has reached a stage where we can actually claim it as a core disease biomarker.
"If you have an increased level of p-tau 231 you are more likely to develop Alzheimer's in the next year."
Finding the marker was one challenge but developing a test for it was another, he says. "It took 10 years to develop a bio-assay to detect the protein. It is very difficult to detect because it is so small and it is not highly concentrated [ in cerebrospinal fluid]."
He knows his test works because of the results from a new international multi-centre study published in the December issue of the journal Neurology.
It followed 145 subjects for 18 months, using Prof Hampel's Elisa (Enzyme-Linked ImmunoSorbent Assay) test to measure p-tau 231 protein levels. The test was able to predict the conversion from preclinical "mild cognitive impairment" (MCI) to Alzheimer's disease. "It had the predictive power of about 80 per cent accuracy across all the centres," Prof Hampel states.
The test is hugely important because it provides an early warning of the presence of Alzheimer's and therefore allows the elimination of other causes of mild cognitive impairment.
No one at the time of discovery believed that his work with p-tau 231 would lead to a new test for Alzheimer's. "This is what it takes, you have to be persistent and then if you are lucky you get these kind of results," he says.
The work continues, however, within the new Alzheimer's research team that links staff in Tallaght Hospital and the TCIN. "We are trying to develop blood markers and we have promising candidates," he states.
"This is the future and we are one of the top five centres worldwide to come up with a promising blood marker and also develop techniques to visualise the physical changes taking place in the brain."
The TCIN has powerful new magnetic resonance imaging devices that can show brain structures in fine detail. Researchers hope to couple p-tau 231 levels, the degree of MCI and changes in the physical brain that will broaden the capacity for early diagnosis.