Studying AGEs and neurodegeneration

This 2022 review suggested more effective ways to conduct in vitro studies of advanced glycation end products (AGEs) and neurodegenerative diseases:

“The main goal of this review was to present and discuss in vitro models that were applied or have the potential to be used in research on AGEs and ND.

  • We introduced and explained current knowledge on AGEs regarding their formation and accumulation in humans.
  • We presented existing evidence linking involvement of AGEs in ND and explained basic concepts of brain physiology and immunology affected by AGEs.
  • We presented and discussed available in vitro models to study AGE-mediated neurodegeneration by dividing them into sections from simple models. These have been applied to more complex models that have not been yet applied in the field of AGEs, but offer opportunities.
  • We gathered advisable in vitro tools based on their relevance to three primary endpoints that AGEs can impact brain pathophysiology and their characteristics and suitability to mimic ND pathophysiology.


Several studies have indicated intracellular formation of AGEs by microglia or neurons, but identification of intracellular AGEs in those cases is made by immunoassays, which have received much criticism regarding their reliability to identify and quantify AGEs. Concerns about these techniques are mostly related to undefined specificity and affinity of anti-AGE antibodies.

The source of observed AGE accumulation in the brain of patients (dietary or endogenous) is not yet fully understood. For that reason, studies on AGE digestion and absorption (i.e., in vitro digestion models) are crucial to understanding the type of dietary AGEs that will circulate and cross the BBB to reach the brain.

On the other hand, endogenous AGEs can also be formed due to increased glucose levels derived from a high glycemic diet. Highly reactive molecules in the brain can contribute to locally produced AGEs extracellularly or intracellularly.

Clinical studies mainly focus on the fate and metabolism of dietary AGEs. Exposure based on consumption of certain foods is difficult to translate to a concentration that cells are going to be exposed to. The complexity and multiple sources of protein glycation require application of in vitro models to understand potential contribution to neurodegeneration.” Vitro Methodologies to Study the Role of Advanced Glycation End Products (AGEs) in Neurodegeneration”

While we’re waiting for research to catch up, we can hedge neurodegenerative disease bets by:

  • Not spiking our blood glucose levels;
  • Avoiding foods with medium and high levels of AGEs;
  • Giving our gut microbiota the intake they need instead of what our unconscious programming dictates; and
  • Maintaining youthful activities.


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