Alzheimer's disease takes a terrible toll on the quality of life for those with the condition, not to mention the demands on their families and carers.
Attempts to find a cure are primarily focused on two types of protein that accumulate in the brain known as plaques and tangles. Understanding the "molecular events" surrounding the disease and, most probably, associated with these accumulations offers significant hope.
In short, once the basic biochemistry is understood, "drug targets" should emerge. Slow destruction of nerve cells in the brain associated with higher mental and emotional function is the disease's hallmark. Associated with this is a build-up of lesions or aggregates characteristic of the disease.
Plaques are composed of a protein fragment, beta-amyloid, which sticks together, surrounds brain cells and is believed to destroy them. Tangles are composed of a structural protein called tau which changes its shape, forming deposits which knot together and build up inside nerve cells, killing them from the inside.
The greater the plaques and tangles, the greater the degree of dementia, though their relationship in terms of causing the disease is not known. Much work, nonetheless, involves trying to unravel events that cause plaques and tangles to build up in Alzheimer's disease and determine how this causes destruction of key nerve cells.
A group at UCC's department of biochemistry, including Dr Cora O'Neill and a PhD student, Ms Mary Kelliher, has discovered that the ability of nerve cells to handle and control calcium is progressively affected as the disease advances.
Details were published recently in Neuroscience. It shows that progressive and slowly developing changes occur in a key protein receptor that works as a channel inside nerve cells and plays a central role in control of calcium release into nerve cells.
"Importantly, these calcium channel changes are only found in areas that degenerate in Alzheimer's disease and link strongly with the development of plaques and tangles," said Dr O'Neill.
This finding could form the basis of a breakthrough in understanding and treatment of the neuro-degeneration which causes the disease. Developing new drugs to reduce or block this impaired calcium release may help combat the progression of Alzheimer's disease.
Calcium acts as a masterswitch in nerve cells "controlling the normal excitability and communication between nerve cells". It also has a prominent role in information-processing carried out by neurotransmitter molecules (which relay electrical signals in chemical form), and in memory formation, she added.
However, if this calcium signal is not controlled properly, high or inappropriate calcium levels can be damaging for nerve cells leading to the activation of "cell death pathways", deregulated information processing and impaired brain function.
It has been a good year for Alzheimer's research, notably for US researchers employed by the Irish-owned Elan Corporation who discovered ways to block beta-amyloid build-up in mice.
But the discovery of the genetic make-up and environmental lifestyle influences that predispose a person to the sporadic form of the disease will be vital to understanding and developing effective therapies, Dr O'Neill believes.
Inheritance of a gene type that encodes a cholesterol-carrying protein increases the probability of developing Alzheimer's disease but does not actually cause it. "Such genes may interact with environmental, lifestyle, or dietary factors to raise the risk of developing the disease as we age," she said.
Drugs already available increase levels of a neurotransmitter which controls memory and cognitive function, known as acetylcholine, and may also prevent beta-amyloid formation. In some patients it can help improve memory and concentration, but they do not seem to stop or block damage to nerve cells, and their benefits only last for up to 18 months.
Exciting discoveries of other potential drug targets, notably stemming from work at UCC, offer the hope of more effective treatments.