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Alzheimer’s may be due to a metabolic disorder

A new American study links Alzheimer's with energy production and consumption.

Alzheimer’s may be due to a metabolic disorder

A team of researchers from McLean Hospital and Harvard Medical School, led by Kai C. Sonntag and Bruce M. Cohen, has found a connection between the interruption of energy production and the late development of Alzheimer’s disease. The results of the research have been published in Scientific Reports.

“This discovery has several implications when it comes to understanding Alzheimer’s and developing potential therapeutic treatments.

Our study maintains the hypothesis that a deficiency in the multiple components that interact in the  bioenergetic metabolism can be a key mechanism in the increase of the risk and the path physiological development of this devastating disease“, says Sonntag, a researcher in stem cells  associated with McLean Hospital and professor of psychiatry at Harvard Medical School.

In the last three decades it was thought that the accumulation of small toxic molecules in the brain called beta-amyloid or APP was decisive for the onset of Alzheimer’s disease. There was determining evidence from the study of   familial or early-onset Alzheimer’s that affected about 5% of the patients and that were related to mutations that gave rise to abnormally high levels of APP in the brain.

However, this hypothesis was insufficient to explain the pathological changes in the most common late-onset Alzheimer’s, which affects more than 5 million elderly people in the United States and a similar number in Europe.

“Since late-onset Alzheimer’s is a disease of aging, many physiological changes related to aging, including those related to metabolism and the production and transformation of energy, could contribute to increasing the risk of suffering from the disease. Bioenergetics is the production, use and exchange of energy between cells and organs and the environment.

The high energy demand of the brain

It is well known that bioenergetic changes occur as they age and affect the whole body, but particularly the brain, which has a high energy demand, “according to Cohen, director of the Neuropsychiatric Research Program at McLean Hospital and Professor of Psychiatry at the Harvard Medical School According to Sonntag and Cohen what is not so clear is which of those changes are active factors and which are a consequence of aging and disease.

In their research, Sonntag and Cohen analyzed the bioenergetic profiles of skin fibroblasts from late Alzheimer’s patients and from healthy people.

They focused particularly on two main components of energy production in cells: glycolysis, which is the metabolic mechanism responsible for oxidizing glucose in order to obtain energy consumption for the mitochondria of the cell; and the expenditure of that energy in the mitochondria through the use of oxygen in the process of oxidative phosphorylation or mitochondrial respiration.

The researchers found that cells with Alzheimer’s showed failures in mitochondrial metabolism and a reduction of molecules important for energy production, such as nicotinamide adenine dinucleotide (NAD).

Fibroblasts from late Alzheimer’s patients also revealed changes in energy production in glycolysis , despite their inability to increase glucose intake in response to insulin IGF-1.

Both the abnormal mitochondrial metabolism and increased glycolysis in cells of late Alzheimer’s patients were the result of disease and not  aging , while the reduction in glucose intake and the inability to respond to IGF-1 were a consequence of both aging as of the disease.

According to Sonntag, “this indicates faults in the mitochondria and memory loss due to the aging cells suffer an increasing oxidative stress that affects the production of mitochondrial energy.”

Since nerve cells in the brain rely almost entirely on mitochondrial energy, when it fails it is particularly damaging to the brain, Cohen says.


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