A neurofibrillary tangle in a nerve cell from the brain of a patient with Alzheimer's disease. The tangle(yellow) lies in the cytoplasm(green) of the cell, and consists of abnormal aggregates of the protein tau.

Thomas Deerinck, NCMIR / photoresearchers.com

2007 has been a good year for Harald Hampel and his Alzheimer's disease research team at the Institute of Neuroscience at Trinity College Dublin (TCD). The team, with its network of international collaborators, has produced a veritable flurry of headline-hitting publications since Hampel arrived from the University of Munich in 2007 to take up the professorship and the chair of psychiatry at Dublin's Adelaide and Meath Hospital.

"It was the state-of-the-art neuroimaging equipment and infrastructure at TCD, and especially the opportunity to collaborate with many other researchers there who are studying aging," explains Hampel's deputy, Arun Bokde. "You need infrastructure and people. Buildings and machines are relatively easy to get, but people are more difficult, and collaborations are really important for multidisciplinary research."

The recent publications brought news of three different biomarkers that could help predict which people with mild cognitive impairment will go on to develop full-blown Alzheimer's disease (AD). First, in June they showed that raised levels of the marker BACE-1 in cerebrospinal fluid correlate well with the presence of the ApoE gene, which is the major genetic risk factor of AD (Arch Gen Psychiatr, 64:718-26, 2007). That was followed by news that a novel measure of brain atrophy seen in structural MRI scans correlates well with the development of the disease (Neuroimage, 38:13-24, 2007).

Then, in December, they reported the first multicenter validation that an existing cerebrospinal fluid biomarker, p-tau (phosphorylated tau protein), can predict the transition from mild cognitive impairment to AD with an average accuracy of 80% (Neurology, 69:2205-12, 2007). These studies reflect the group's multipronged approach to addressing the challenges of AD, which affects about 3% of people aged 65 to 74, and nearly half of those aged over 85.

Despite being common, AD remains poorly understood. "There are two main hypotheses," explains Bokde: One is that beta-amyloid causes cell death; the other is that neurofibrillary tangles cause the problem. "We're utilizing biomarkers for both, so we're not committed either way at this point, although probably beta-amyloid has the upper hand."

The first symptoms of mild cognitive impairment can be worrying, but according to Michael Ewers, a senior scientist with Hampel's team, only 15% of people with mild cognitive impairment will develop full-blown AD, while 20% revert to normal. Hence, there is an urgent need for accurate and cost-effective diagnostic and predictive tests. "A blood test would be really useful in clinical diagnosis for patients, but also for us in research, as we would be able to identify patients earlier and stratify them in terms of risk," Bokde says.

Hampel's group has received funds from the US National Institutes of Health and the US Alzheimer's Association, the Federal Ministry of Education and Research in Germany, Science Foundation Ireland, and Ireland's Health Research Board. Hampel is quick to praise the resources available at both AmiNCH (the Adelaide and Meath Hospital incorporating the National Children's Hospital) and TCD's Institute of Neuroscience.

One important factor has been access to patients at the community level in the hospital. As Bokde explains: "You see a broader group of patients than you would in a typical research group, and many of them have other diseases. And interesting patients make for interesting research." Plus, TCD receives the latest equipment from manufacturers, such as Philips and Brucker, "and that makes our research easier."

Hampel is also a principal investigator with the European Alzheimer's Disease Neuroimaging Initiative (E-ADNI), a network based on the US ADNI model directed by Michael Weiner of the University of California, San Francisco. Weiner praises the Dublin team's work as "cutting-edge, state-of-the-art research on the mechanisms of Alzheimer's disease [that] may lead to development of new treatments and methods for early detection. Taken together, these efforts will significantly advance the world-wide efforts to develop effective treatments and prevention of Alzheimer's disease."