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Cell-Killing Acid Found in Brains of All Dementia Patients

May serve as guide to new drug treatments for Alzheimer’s

Aug. 5, 2005 – An acid that kills nerve cells in the brain, quinolinic acid, was found in all the brains of dementia patients tested in a recent study released today, which the Australian researchers say suggests the toxin plays an important role in the progression of Alzheimer's disease (AD), the most common form of dementia.

They say their finding is significant because it may provide evidence that could lead drug developers who are working on drugs for other conditions to investigate their use for Alzheimer’s patients to halt progression of the disease.

Current drug are only minimally effective treatments for the condition, which is increasing with the aging population.

"We found that all of the brains of dementia patients showed quinolinic acid neurotoxicity," said Professor Bruce Brew, Director of Neurology at St Vincent's Hospital and Professor of Medicine at the University of New South Wales (UNSW). "This acid kills nerve cells in the brain, leading to brain dysfunction and ultimately death."

"Quinolinic acid is part of a biochemical pathway called the kynurenine pathway," said the lead author of the research, UNSW's Dr Gilles Guillemin, who is based at the Centre for Immunology at St Vincent's Hospital. "The activation of that pathway is also found in other major brain diseases including Huntington's disease, stroke, dementia and schizophrenia."

The paper Indoleamine 2, 3 dioxygenase and quinolinic acid Immunoreactivity in Alzheimer's disease hippocampus has been published this week in the leading international journal Neuropathology and Applied Neurobiology. It is the result of collaboration between researchers from St Vincent's Hospital, UNSW, the University of Sydney and Hokkaido University, Japan.

"There are several drugs which can block this pathway, which are already under investigation by our laboratory and others," said Dr Guillemin.

The drugs, which would need to be tested for efficacy, could be used to complement other treatments.

"Quinolinic acid may not be the cause of Alzheimer's disease, but it plays a key role in its progression," said Alzheimer's researcher, Dr Karen Cullen from the University of Sydney. "It's the smoking gun, if you like.

"While we won't be able to prevent people from getting Alzheimer's disease, we may eventually, with the use of drugs, be able to slow down the progression."

The other researchers are Claire Noonan from Sydney University and Osamu Takikawa from Hokkaido University, Japan.

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