22 January 2007

Clues to the origin of dementia

Oxidative stress associated with dementia may be a cause and not an effect of Alzheimer's, suggests a study with fruit flies from the US.

Oxidative stress associated with dementia may be a cause and not an effect of Alzheimer's, suggests a study with fruit flies from the US.

The research gives great hope to a dietary/nutritional approach to improve brain health and curb the rise in Alzheimer’s and dementia around the world.

“This is exciting because antioxidants may prove to be a good therapeutic approach to [prevent] Alzheimer's disease and ameliorate human neurodegeneration,” said lead author Dora Dias-Santagata in a statement.

Although the mechanism of Alzheimer’s is not clear, more support is gathering for the build-up of plaque from protein deposits. The deposits are associated with an increase in brain cell damage and death from oxidative stress.

Cause or result?
However, whether oxidative stress is a cause or a result of disease is not clear, said the researchers behind the new study.

“In this study, we provide substantial in vivo evidence supporting a causative role for oxidative stress in tau [protein]-induced neurodegeneration,” wrote Dias-Santagata in The Journal of Clinical Investigation.

The fundamental research, by scientists from Brigham and Women’s Hospital and Harvard Medical School in Boston and Howard University in Washington, used genetic and pharmacological approaches to change the genetic expression of transgenic fruit flies so that they would express a disease-related mutant form of human tau protein.

Two different approaches was used by the researchers - on the one hand they manipulated genes responsible for the production of anti-oxidant proteins and on the other hand administered the potent anti-oxidant vitamin E to the mutant flies.

Two anti-oxidant proteins involved
The US-based researchers report that reduction in the activity of two anti-oxidant proteins - superoxide dismutase (SOD) and thioredoxin reductases (Trxr) – as a result of their genetic manipulation led to increasing neurodegeneration in the brain of the mutant flies, while administration of vitamin E reversed the effect.

Control flies that did not express the human tau protein did not show any signs of neurodegeneration, they said.

Both results are said to indicate that oxidative stress plays an important role in neurodegenerative dementias, at least in those where the tau protein is involved, and could therefore offer a nutritional/dietary approach to improving brain health.

“Our results suggest that increased levels of oxidative stress play an active role in enhancing tau-mediated neurodegeneration, possibly through cell cycle activation, underscoring the therapeutic potential of targeting antioxidant pathways and cell cycle mechanisms for the [prevention] of AD,” concluded the researchers.

Further research necessary
It must be stressed that significant further research is necessary to study this effect and whether such a mechanism is also observed in humans.

Increasing numbers of studies are reporting that a diet rich in antioxidants from vegetables, and fruit like berries and pomegranate, are associated with a significantly decreased risk of cognitive decline and dementia. - (Decision News Media, January 2007)

Read more:
Alzheimer's Centre
New dementia gene discovered


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