two researchers in a lab

APOE4 and Alzheimer’s - research background

Alzheimer’s disease (AD), a debilitating neurodegenerative disorder, affects approximately 10% of people over the age of 65 worldwide. The disease’s prevalence and impact on cognitive function make it a critical area of study in biomedical research. Our research group, Mitochondria, Health & Longevity in Biogipukoa Heath Research Institute has long been dedicated to understanding the intricate relationships between nutrients, cholesterol, and mitochondrial function, particularly in the context of neurodegenerative disorders like AD. One of the focal points of the research group is the APOE4 variant, a prominent genetic risk factor for AD. With the assumption that APOE4 induces mitochondrial abnormalities, contributing to the pathogenesis of AD, the group has been studying astrocytes that carrying APOE3 and APOE4 variants, cells that support neurons in the brain. MITGEST Doctoral Candidate (DC7), Seungtae Lee, shares insights into the research and elaborates on the benefits from the initial results.

Research goals and methods

Our latest study aims to elucidate the metabolic characteristics of the APOE4 variant and its implications for AD. Utilizing the knowledge acquired during our Seahorse training in the first MITGEST week last year in Udine, we decided to first conduct Seahorse flux analysis on APOE3 and APOE4 astrocytes to investigate their metabolic characteristics. The Seahorse analyzer allows for real-time measurement of cellular metabolism, providing insights into mitochondrial function. By performing a mitochondrial stress test, we aimed to discern any metabolic disparities between the APOE3 and APOE4 variants.

Our initial tests showed that APOE4 astrocytes consume less oxygen compared to APOE3 astrocytes. This lower oxygen consumption suggests that APOE4 astrocytes might be less efficient at producing energy.

We discovered several important differences:

  • Energy Production: APOE4 astrocytes had lower energy production levels, both in normal and stressful conditions. This could mean they struggle more to generate the energy needed for healthy brain function.
  • Efficiency in Energy Use: Despite lower energy production, APOE4 astrocytes seem to use the available energy more efficiently, possibly to compensate for their limitations.


These findings indicate that APOE4 astrocytes have altered mitochondrial function, which could play a role in the development and progression of AD. Understanding these changes is crucial as it may help us identify new targets for treatment.


Our research highlights the interesting role of mitochondrial function in the context of APOE4 astrocytes and AD. By understanding the metabolic alteration caused by the APOE4 variant, we might be able to pave the way for developing targeted therapies that address these specific abnormalities. The journey toward effective AD treatments is challenging, but with continued research and collaboration, we can hope to make meaningful progress in combating this devastating disorder.

We encourage the scientific community and the public to stay informed about the latest advancements in mitochondrial research. You can follow our progress and access more detailed information through our website and social media accounts. Together, we can make significant strides toward understanding and combating this debilitating disease.

The news item was written by MITGEST DC7 Seungtae Lee

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