A Queen's Unversity researcher is working on a new predictive test for Alzheimer's disease, writes Cormac Sheridan
An early diagnostic test for Alzheimer's disease is the research goal of a newly qualified doctor from Coalisland, Co Tyrone. Dr Bernadette McGuinness, a 2006 graduate of Queen's University, Belfast, who is completing her clinical training this summer, started work on the project about a week ago, backed by £228,000 (€339,000) in funding from the US-based Paul B Beeson Career Development Awards In Aging Research Program.
McGuinness is the first recipient in Ireland of a Beeson award, following an extension of the programme to Ireland this year. Named after the distinguished US physician, who died last August at the age of 97, the scheme supports the development of young physician scientists specialising in aging research and geriatric medicine.
Atlantic Philanthropies, the foundation established by the Irish-American philanthropist Chuck Feeney, is one of the backers of the initiative in the US and is the sole funder of the program in Ireland.
McGuinness, her research mentor Peter Passmore and colleagues Janet Johnston and David Craig in the neuroscience research group at QUB, will study activity levels of an enzyme called beta secretase in patients with mild cognitive impairment, a condition that often develops into Alzheimer's.
Alzheimer's is characterised by a progressive deterioration of the brain, due to the abnormal accumulation and deposition of two protein-based aggregates, known as amyloid plaques and neurofibrillary tangles. Beta secretase is thought to play a key role in the disease process, as it cleaves a protein called amyloid precursor protein to form a smaller molecule known as amyloid beta peptide, the main constituent of the amyloid plaques.
Inhibiting beta secretase activity is a major theme within Alzheimer's drug research at present. But McGuinness and her colleagues are examining the role of the enzyme from an alternative standpoint, as a potential marker of early disease.
Their work is building on an initial observation of Johnston's that activity levels of beta secretase are significantly elevated in the platelets (a type of blood cell) of patients with Alzheimer's disease, compared with those of healthy controls. "We're not sure why that happens," says McGuinness.
The brain functioning of the same patients was also assessed, using a test called the mini mental state examination (MMSE). "The scores didn't correlate with [beta secretase] activity in Alzheimer's patients, so we wondered if activity went up before dementia was manifest in the patients," McGuinness says. This was subsequently confirmed in a preliminary, small-scale study of patients with mild cognitive impairment.
To further extend that finding, the QUB group now plans to recruit 150 subjects with mild cognitive impairment, via the memory clinic at Belfast City Hospital, a QUB teaching hospital. These, along with 150 healthy controls, will be assessed on the basis of their blood platelet beta secretase activity, their performance in several brain function tests and their brain activity, measured using an imaging technique called Positron Emission Tomography (Pet). The participants will be followed up 12 and 24 months after their initial exam.
The data should deliver some important insights on whether platelet beta secretase levels, which can be measured from a simple blood sample, can reliably predict the onset of Alzheimer's.
At present, the condition can only be definitively confirmed by a post-mortem brain examination. Although the cognitive tests that are used on suspected cases are about 90 per cent accurate, the disease is usually well under way at that point. "By the time people present to memory clinics, a lot of the damage has been done. The plaques are there," says McGuinness.
Early diagnosis would aid decision-making and would allow patients themselves to become more involved in planning their futures. As drug therapies for Alzheimer's improve - currently available treatments offer limited benefits - early diagnosis will be even more critical, as early intervention could help to delay the onset of this most devastating condition. "It would be very exciting if it works," McGuinness says.