Amino acid supplementation could restore memory in Alzheimer's patients

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A new study in mice has revealed the metabolic pathway that contributes to memory loss in Alzheimer's disease and found that supplying a specific amino acid as a nutritional supplement can restore spatial memory.

The team of scientists from the University of Paris-Saclay and the University of Bordeaux say their new findings show this nutritional supplement could be a promising compound for reducing memory loss related to Alzheimer's, as well as Parkinson's and Huntington's.

The study report, published in Cell Metabolism, points out that brain uses a large part of the energy available to our body. To work properly, neurons and the surrounding cells, particularly astrocytes, must cooperate.

A decrease in regional brain glucose consumption is observed in early Alzheimer’s disease, decades before neuronal death and clinical symptoms occur. But until now it has been unknown whether this deficit contributed directly to the cognitive symptoms of Alzheimer's disease. 

Researchers in this study used a mouse model of Alzheimer’s disease to identify a mechanistic link that connects defective glycolysis in astrocytes to impaired l-serine production and reduced neuronal function and subsequently found that supplementation with l-serine can rescue the cognitive deficits. 

The metabolic pathway

Researchers found that mice with Alzheimer's disease a decrease in the use of glucose by astrocytes reduces L-serine production. This amino acid is mainly produced by these brain cells and its biosynthesis path is altered in patients.

L-serine is the precursor of D-serine, known to stimulate NMDA (N-methyl-D-aspartate) receptors, essential for brain function and to the establishment of memory. So by producing less L-serine, astrocytes cause reduced activity in these receptors, which alters neuronal plasticity and the associated memorisation capacities.

With the identification of the role of L-serine in memory disorders and the experimental efficacy of nutritional supplementation, new strategies appear that may compliment medical treatment, to combat early symptoms of Alzheimer's disease and other diseases that display metabolic deficits, like Parkinson's and Huntington's.

The researchers in the study suggest that, since L-serine is available as a nutritional supplement, this compound should be rigorously tested in humans, through controlled clinical trials.

Source: Cell Metabolism

Le Douce. J., et al

"Impairment Of Glycolysis-Derived L-Serine Production In Astrocytes Contributes To Cognitive Deficits In Alzheimer'S Disease" 

DOI: 10.1016/j.cmet.2020.02.004