Is Alzheimer’s Disease Driven by Our Foraging Instinct?

A new study from the University of Colorado, published in The American Journal of Clinical Nutrition, has proposed that Alzheimer’s disease (AD) is a result of an evolutionary survival pathway used during times of scarcity and is driven by diet.

Foraging to survive

To protect themselves from starvation when food was scarce, early humans developed a survival response – go foraging. Foraging requires focus, quick thinking, risk-taking and other behaviors that are enhanced when metabolism in specific brain areas is inhibited. The new paper, led by professor of medicine Dr. Richard Johnson, proposes that this survival mechanism is initiated through the consumption or production of fructose.

Fructose and its metabolic byproduct, intracellular uric acid, reduce blood flow to the brain’s cerebral cortex, hippocampus and thalamus, enhancing foraging behavior by blocking non-essential activity, such as paying attention to time and recent memories. They also increase blood flow around the visual cortex associated with food reward. This metabolic response is hypothesized by Johnson and colleagues to play a role in the pathology of AD.

“We believe that initially the fructose-dependent reduction in cerebral metabolism in these regions was reversible and meant to be beneficial,” Johnson said. “But chronic and persistent reduction in cerebral metabolism driven by recurrent fructose metabolism leads to progressive brain atrophy and neuron loss with all of the features of AD.”

Johnson proposes that modern-day living, with diets containing high fat, sugary and salty foods, has resulted in the foraging survival pathway getting “stuck” in an on mode. The fructose in the brain as a result of the activated pathway leads to inflammation and eventually AD.

“A study found that if you keep laboratory rats on fructose long enough they get tau and amyloid beta proteins in the brain, the same proteins seen in AD,” Johnson commented. “You can find high fructose levels in the brains of people with AD as well.”

What does this mean for Alzheimer’s disease research?

By making the case that Alzheimer’s is a disease driven by diet, the researchers have offered a new lens through which to view the disease.

Johnson states that further research into the role of fructose and uric acid metabolism in AD is needed. He suggests that dietary and pharmacological trials to reduce or block fructose metabolism would determine whether this is a possible avenue for the prevention, management or treatment of AD.

Reference: Johnson RJ, Tolan DR, Bredesen D, et al. Could Alzheimer’s disease be a maladaptation of an evolutionary survival pathway mediated by intracerebral fructose and uric acid metabolism? Am J Clin Nutrit. 2023. doi: 10.1016/j.ajcnut.2023.01.002

This article is a rework of a press release from the University of Colorado. Materials have been edited for length and content.