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Alzheimer’s disease: key cause and possible treatment identified

31 October 2019 | Research - Impact

A team led by Asst Prof Gruber (2nd from right) has found evidence that metabolic dysfunction might be a key cause of Alzheimer’s disease

A study by a Yale-NUS College research team has found evidence that a key cause of Alzheimer’s disease is metabolic dysfunction, and has identified a common anti-diabetes drug, Metformin, that can potentially be used as treatment.

The most common neurodegenerative disease affecting the elderly worldwide, Alzheimer’s disease is also one of the most prevailing causes of dementia. Unfortunately, despite more than twenty years of worldwide research effort, scientists have yet to identify the exact cause of Alzheimer’s and no proven treatment is available.

Scientists currently have two competing theories for the possible cause of Alzheimer’s disease. The first purports that the accumulation of a specific protein called amyloid-beta protein in the brain is the primary cause; while a second, more recent theory proposes that metabolic dysfunction - specifically a dysfunction of mitochondria, the cell’s energy-producing machinery - is responsible.

In the studies led by Assistant Professor of Science (Biochemistry) Jan Gruber, the team discovered that metabolic defects occur well before any significant increase in the amount of amyloid-beta protein was detected. Additionally, further studies showed that when a common anti-diabetes drug called Metformin was used as treatment, these metabolic defects could potentially be reversed.

“Current trials of Alzheimer’s drugs targeting proteins have failed despite billions of dollars being invested. Based on the emerging strong links between mitochondrial dysfunction and Alzheimer’s pathology, it might be better to adopt a preventative strategy by targeting metabolic defects, especially mitochondrial defects, directly and early, well before protein aggregates are even present,” said Asst Prof Gruber.

He suggested that metabolic and mitochondrial dysfunctions should be viewed as fundamental features of ageing in general and that age-dependent diseases, including Alzheimer’s, should thus be viewed as manifestations of ageing. Hence, it may be easier to prevent or treat age-dependent diseases by targeting the mechanisms of ageing rather than by treating individual diseases after symptoms occur.

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