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 disruption 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 for understanding Alzheimer’s and developing potential therapeutic treatments .
Our study hypothesizes that a deficiency in the multiple components that interact in bioenergetic metabolism may be a key mechanism in the increased risk and pathophysiological development of this devastating disease, “says Sonntag, a stem cell researcher 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 appearance of Alzheimer’s disease. There was strong evidence from the study of familial or early-onset Alzheimer’s that affected about 5% of patients and was related to mutations that resulted in 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 disease, 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 an increased 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 with aging and affect the entire 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 these changes are active factors and which are a consequence of aging and disease.
In their research, Sonntag and Cohen analyzed the bioenergetic profiles of fibroblasts from the skin of patients with late Alzheimer’s disease and healthy people .
They particularly focused on two main components of energy production in cells: glycolysis, which is the metabolic mechanism responsible for oxidizing glucose in order to obtain energy for consumption by the cell’s mitochondria; 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 in 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 the increased glycolysis in cells of late Alzheimer’s patients were the result of the disease and not of 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 mitochondrial failure and memory loss due to aging cells undergoing increased oxidative stress that affects mitochondrial energy production .”
Since nerve cells in the brain are almost entirely dependent on mitochondrial energy, when it fails it is particularly damaging to the brain , Cohen says.
Article reference:
Kai-C. Sonntag, Woo-In Ryu, Kristopher M. Amirault, Ryan A. Healy, Arthur J. Siegel, Donna L. McPhie, Brent Forester & Bruce M. Cohen. ‘Late-onset Alzheimer’s disease is associated with inherent changes in bioenergetics profiles’. Scientific Reports 7, Article number: 14038 (2017). Doi: 10.1038 / s41598-017-14420-x
