Metabolic Defects Precede Alzheimer’s Disease, Study Finds

Researchers in Singapore have discovered that defects in cellular metabolism become detectable before the appearance of protein plaques characteristic of Alzheimer’s disease.

AsianScientist (Dec. 27, 2019) – An international team of scientists has found evidence that metabolic dysfunction is a primary cause of Alzheimer’s disease. They published their findings in the journal eLife.

Alzheimer’s disease is the most common neurodegenerative disease affecting the elderly worldwide, as well as one of the most common causes of dementia. In Singapore, one in ten people aged 60 or above is believed to suffer from dementia. After more than twenty years of research effort worldwide, scientists are still unable to identify the exact causes of Alzheimer’s and no proven treatment is available.

Two competing theories are currently proposed to explain the cause of Alzheimer’s disease: the first is focused on the accumulation of a specific protein, called amyloid-beta protein, in the brain. The second and more recent theory proposes that metabolic dysfunction—specifically, a dysfunction of the cell’s energy-producing machinery called mitochondria—is responsible.

Using the worm Caenorhabditis elegans as a model organism, researchers led by Assistant Professor Jan Gruber at the Yale-National University of Singapore College have discovered that metabolic defects occur well before any significant increase in the amount of amyloid-beta protein is detected.

For example, the team detected abnormalities in the relative quantities of amino acids and triglycerides—subunits that make up proteins and fatty acids, respectively—in worms that eventually went on to accumulate amyloid-beta plaques. Importantly, when the researchers treated worms with a common anti-diabetes drug called metformin, they were able to reverse the metabolic defects and normalize the worms’ healthspan and lifespan.

“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 Gruber.

He added that metabolic and mitochondrial dysfunctions should be viewed as fundamental features of aging in general, and that age-dependent diseases, including Alzheimer’s disease, should therefore 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 treating individual diseases after symptoms occur, he said.

The article can be found at: Teo et al. (2019) Metabolic Stress is a Primary Pathogenic Event in Transgenic Caenorhabditis elegans Expressing Pan-neuronal Human Amyloid Beta.


Source: National University of Singapore; Photo: Shutterstock.
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