4th August 1999

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The brain's efforts to defend itself against the onset of Alzheimer's disease may actually make the disease worse, according to University of Ulster researchers.

But their work also offers hope of finding a way to halt the progression of this debilitating condition, says researcher Dr Eugene O'Hare.

It's almost 100 years since Alois Alzheimer first identified the disease that carries his name - but there's still no effective intervention strategy.

One of the characteristics of the disease is the formation of plaques - composed of beta-amyloid protein - in the sufferer's brain. Until recently, research had been held back by science's inability to replicates the chemical structure of these beta-amyloid plaques.

But today, researchers can simulate in the laboratory the chemistry of the plaques found in the brains of Alzheimer's' disease sufferers, and laboratory work on understanding how they act is proceeding apace.

Building on that advance, Dr O'Hare and his team found that, for rats, it takes around 35 days after being injected with the simulated plaque material for the animals to show any sign of impaired functioning.

After many tests, they realised that, in fact, it was taking the 35 days for the rats' immune systems to begin to combat the new substance.

Dr O'Hare takes up the story: "What we found was that after 35 days, the rat's immune systems finally woke up to the presence of the amyloid, and started to produce astrocytes and microglia to attack the plaque.

"The astrocytes try to wall off the amyloid, blocking it off so it cannot spread any further throughout the tissue: the microglia ingest the amyloid, carrying it out of the system.

"But when the astracytes and the microglea come into contact with the amyloid, they get sick, and when they get sick, they begin to produce a range of neurotoxins, like inflammatory cytokines and inducible nitric oxide synthase.

And these toxins, which the brain's immune system is producing in response to the amyloid, are washing over the surrounding neurons. These neurons in turn begin to sustain damage from the toxins, and start to die, producing adverse effects in the host creature.

"Most probably, the amyloid itself has a minimal effect on the neurons, especially in the early stages of the disease: in fact, it's the immune system's efforts to help which are causing a bigger problem," said Dr O’Hare.

This was an exciting discovery for the research team. In recent years, epidemiological studies have found that people suffering from chronic arthritis -- who took anti-inflammatory drugs over a prolonged period of time - had a significantly lower incidence of Alzheimer's' than the general population.

Building on their discovery about the action of the immune system, the University of Ulster researchers treated further animals with ibuprofen, an anti-inflammatory drug,and found that, up to 90 days after injection, the animals treated with ibuprofen did not develop any impairments.

"The anti-inflammatory drug protected them from the memory and learning deficits that occur normally when they are untreated." said Dr O'Hare. "It was the vital clue we needed."

Dr O'Hare's team are now refining their studies, treating some rats with non-steroidal anti-inflammatory drugs, others with steroids, and others with immune system suppressants.

Work revolves around experiments to discover which way of slowing down the inflammation or blocking the immune response gives the greatest protection against the behavioural detriments normally associated with the presence of Alzheimer plaques in the brain.

For further information, please contact:

Press Office Department of Communication and Development
Telephone: 028 9036 6178
Email: pressoffice@ulster.ac.uk