Alzheimer’s disease remains incurable, despite the best efforts of scientists and a number of recent discoveries.
Researchers now have a new hypothesis about a possible driving force behind the disease: a type of sugar called fructose.
Previous research has indicated that fructose in the brain helped our ancestors search for food. But the new paper suggests that, in our modern world, the changes triggered by this sugar may actually be linked to Alzheimer’s disease.
Fructose is found in many foods, such as fruits, vegetables, and honey.
But it can also be produced naturally by the body, for example through pathways stimulated by the consumption of a high-salt diet.
So how did fructose help our ancestors? Sugar inhibits certain parts of the brain’s metabolism: blocking out distractions, such as recent memories and paying attention to the passage of time.
This “deactivation” of certain brain activities helps us focus better on survival, and also encourages exploration and risk-taking behaviors, all of which are important for foraging.
In the latest study, the researchers claim that this “survival switch” is now permanently on, even though most of us do very little foraging these days.
This causes us to eat more high-fat, sweet, and salty foods than necessary to produce more fructose.
And that in turn could lead to brain inflammation and, ultimately, the conditions that cause Alzheimer’s disease, the scientists propose.
“We believe that initially, the fructose-dependent reduction in brain metabolism in these regions was reversible and expected to be beneficial,” says Richard Johnson, a nephrologist at the University of Colorado Anschutz Medical Center.
“But a chronic and persistent reduction in brain metabolism driven by recurrent fructose metabolism leads to progressive brain atrophy and loss of neurons with all the hallmarks of Alzheimer’s disease.”
This latest study does not include any new laboratory research, but it neatly connects the dots between previous studies, including those linking fructose to survival and linking fructose to Alzheimer’s disease.
Researchers hypothesize that the effects of fructose and its byproduct, intracellular uric acid, are behind the protein buildup linked to Alzheimer’s disease.
These effects include reduced blood flow to the cerebral cortex, hippocampus, and thalamus, and increased blood flow around the visual cortex (linked to food reward cues).
This could occur in particular by the failure of brain cells called astrocytes, which can lead to the accumulation of amyloid plaque linked to Alzheimer’s disease.
Researchers also point to associations between various Alzheimer’s risk factors (such as alcohol consumption) and fructose production, as well as animal studies.
“One study found that if you keep lab rats on fructose long enough, they get tau and beta-amyloid proteins in the brain, the same proteins seen in Alzheimer’s disease,” Johnson says. “You can also find high levels of fructose in the brains of people with Alzheimer’s disease.”
The next step is to perform further tests to determine the role of fructose and uric acid metabolism in the brain and how this might lead to the conditions associated with Alzheimer’s disease.
“We claim that Alzheimer’s disease is caused by diet,” Johnson says.
“We suggest that dietary and pharmacological trials aimed at reducing fructose exposure or blocking fructose metabolism be performed to determine if there is any potential benefit in the prevention, management, or treatment of this disease.”
The research was published in the American Journal of Clinical Nutrition.