Smoking gun for Alzheimer’s disease: Quinolinic acid

In a world first, Australian researchers have found a toxin that plays an important role in the progression of Alzheimer’s disease (AD), the most common cause of dementia.

The research is significant because drugs that are in the advanced developmental phase for other conditions might be able to be used on Alzheimer’s patients, to halt the disease progressing. At present, there are only minimally effective treatments for the condition, which is increasing with the ageing 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.”

There are currently more than 200, 000 people with Alzheimer’s disease in Australia. The number will exceed 730, 000 by 2050.

“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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1 thought on “Smoking gun for Alzheimer’s disease: Quinolinic acid”

  1. You would serve readers better by a more skeptical attitude. This paper is a small byte of information, not remotely a smoking gun. It’s a small study of only 6 brains without co-existing vascular disease or Lewy body disease. People have known about quinolinic acid for more than 20 years. It can kill neurons; inflammatory stimuli such as bacterial endotoxin increase the activity of the enzyme indoleamine dioxygenase (IDO) responsible for its synthesis. Inflammation is part of Alzheimer’s disease but a. hardly anyone thinks that inflammation is primary b. reducing inflammation upstream of IDO may be better because quinolinic acid is only one of many inflammatory mediators which hurt brain (“the dark side of glia”). Recognize the fact that authors have strong incentives to hype marginal findings. Anti-inflammatory treatments may prove beneficial in Alzheimer’s and drugs which inhibit the IDO enzyme may be useful but are remote from clinical trials. This paper is better than the thimerosal-autism hokum but scientific evidence is a mosaic of many tiny pieces, which must be placed in perspective. Breakthroughs are rare, media hype is common.
    Bob Snodgrass
    Torrance, CA
    Neurologist, neuroscientist

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