Resting-state brain signal complexity discriminates young healthy APOE e4 carriers from non-e4 carriers

Xiaojing Li, Yadwinder Kaur, Oliver Wilhelm, Martin Reuter, Christian Montag, Werner Sommer, Changsong Zhou*, Andrea Hildebrandt*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review


It is well established that the e4 allele of the APOE gene is associated with impaired brain functionality and cognitive decline in humans at elder age. However, it is controversial whether and how the APOE e4 allele is associated with superior brain function among young healthy individuals, thus indicates a case of antagonistic pleiotropy of APOE e4 allele. Signal complexity is a critical aspect of brain activity that has been associated with brain function. In this study, the multiscale entropy (MSE) of resting-state EEG signals among a sample of young healthy adults (N = 260) as an indicator of brain signal complexity was investigated. It was of interest whether MSE differs across APOE genotype groups while age and education level were controlled for and whether the APOE genotype effect on MSE interacts with MSE time scale, as well as EEG recording condition. Results of linear mixed models indicate overall larger MSE in APOE e4 carriers. This genotype-dependent difference is larger at high as compared with low time scales. The interaction effect between APOE genotype and recording condition indicates increased between-state MSE change in young healthy APOE e4 carriers as compared with non-carriers. Because higher complexity is commonly taken to be associated with better cognitive functioning, the present results complement previous findings and therefore point to a pleiotropic spectrum of the APOE gene polymorphism.
Original languageEnglish
Pages (from-to)854-866
Number of pages13
JournalEuropean Journal of Neuroscience
Issue number5
Early online date19 Jan 2023
Publication statusPublished - 3 Mar 2023

User-Defined Keywords

  • APOE gene
  • antagonistic pleiotropy
  • brain signal complexity
  • cognitive decline
  • e4 allele
  • multi-scale entropy (MSE)
  • resting state


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