Circulating Glutamine and Alzheimer's Disease: A Mendelian Randomization Study

Clin Interv Aging. 2020 Feb 10:15:185-193. doi: 10.2147/CIA.S239350. eCollection 2020.

Abstract

Background: Alzheimer's disease is a devastating neurodegenerative disorder. Its worldwide prevalence is over 24 million and is expected to double by 2040. Finding ways to prevent its cognitive decline is urgent.

Methods: A two-sample Mendelian randomization study was performed instrumenting glutamine, which is abundant in blood, capable of crossing the blood-brain barrier, and involved in a metabolic cycle with glutamate in the brain.

Results: The results reveal a protective effect of circulating glutamine against Alzheimer's disease (inverse-variance weighted method, odds ratio per 1-standard deviation increase in circulating glutamine = 0.83; 95% CI 0.71, 0.97; P = 0.02).

Conclusion: These findings lend credence to the emerging story supporting the modifiability of glutamine/glutamate metabolism for the prevention of cognitive decline. More circulating glutamine might mean that more substrate is available during times of stress, acting as a neuroprotectant. Modifications to exogenous glutamine may be worth exploring in future efforts to prevent and/or treat Alzheimer's disease.

Keywords: Alzheimer’s disease; Mendelian randomization; dementia; glutamine; metabolism; prevention.

MeSH terms

  • Aged
  • Alzheimer Disease* / blood
  • Alzheimer Disease* / metabolism
  • Blood-Brain Barrier / physiology*
  • Brain / metabolism*
  • Cognition / physiology
  • Cognitive Dysfunction / prevention & control*
  • Female
  • Genome-Wide Association Study / statistics & numerical data
  • Glutamine* / blood
  • Glutamine* / genetics
  • Glutamine* / metabolism
  • Humans
  • Male
  • Mendelian Randomization Analysis / methods
  • Neuroprotective Agents / metabolism
  • Receptors, Glutamate / metabolism

Substances

  • Neuroprotective Agents
  • Receptors, Glutamate
  • Glutamine