Palmitic Acid Linked to Alzheimer's Disease via Tau Protein Modifications

Strategic Insights -

A new study has discovered a mechanism by which saturated fatty acids, such as palmitic acid (PA), contribute to the development of Alzheimer's disease (AD). The research, conducted at the National Autonomous University of Mexico (UNAM), found that PA induces insulin resistance, increases intracellular calcium and reactive oxygen species (ROS) production, and reduces the NAD+/NADH ratio in neurons. This disruption leads to decreased activity of the deacetylase Sirtuin1 (SIRT1) and affects signaling pathways that impact the posttranslational modifications (PTMs) of the tau protein. The study also identified changes in the phosphorylation state of several AD-related sites, including S199/202 and S214, which were mediated by the dysregulated activity of the kinases GSK3 beta and mTOR. PA was found to increase the acetylation of residue K280 and elevate total tau level after long exposure time.

Key Takeaways:

  • Palmitic acid (PA) has been linked to Alzheimer's disease (AD) via its ability to induce insulin resistance, increase intracellular calcium and ROS production, and reduce the NAD+/NADH ratio in neurons.
  • The study found that PA disrupts the activity of the deacetylase Sirtuin1 (SIRT1) and affects signaling pathways that impact the posttranslational modifications (PTMs) of the tau protein.
  • Changes in the phosphorylation state of several AD-related sites, including S199/202 and S214, were observed in response to PA exposure.
  • The study identified a mechanism by which PA increases the acetylation of residue K280 and elevates total tau level after long exposure time.
  • The research was funded by the Consejo Nacional de Ciencia y Tecnologia (CONACyT) and conducted at the University of Mexico.
  • Clorinda Arias led the research team, which included researchers from the Institute of Biomedical Research.
  • The study has been peer-reviewed and published in the journal Molecular Neurobiology.

Statistics:

  • 61: The issue number in which the study was published (Molecular Neurobiology).
  • 8: The volume number in which the study was published (Molecular Neurobiology).
  • 5129-5141: The page range in which the study was published (Molecular Neurobiology).
  • 2024: The year in which the study was published.

Sources:

  • Palmitic Acid Induces Posttranslational Modifications of Tau Protein In Alzheimer's Disease-related Epitopes and Increases Intraneuronal Tau Levels. Molecular Neurobiology, 2024;61(8):5129-5141.
  • NewsRx. Studies from National Autonomous University of Mexico (UNAM) Describe New Findings in Alzheimer Disease (Palmitic Acid Induces Posttranslational Modifications of Tau Protein In Alzheimer's Disease-related Epitopes and Increases Intraneuronal ...). Obesity & Diabetes Week. October 13, 2025; p 161.