Open Access

Silke M. Wortha, Stefan Frenzel, Martin Bahls, Mohamad Habes, Katharina Wittfeld, Sandra Van der Auwera, Robin Bülow, Stephanie Zylla, Nele Friedrich, Matthias Nauck, Henry Völzke, Hans J. Grabe, Claudia Schwarz, Agnes Flöel

• Introduction Supplementation with spermidine may support healthy aging, but elevated spermidine tissue levels were shown to be an indicator of Alzheimer's disease (AD). Methods Data from 659 participants (age range: 21–81 years) of the population-based Study of Health in Pomerania TREND were included. We investigated the association between spermidine plasma levels and markers of brain aging (hippocampal volume, AD score, global cortical thickness [CT], and white matter hyperintensities [WMH]). Results Higher spermidine levels were significantly associated with lower hippocampal volume (ß = −0.076; 95% confidence interval [CI]: −0.13 to −0.02; q = 0.026), higher AD score (ß = 0.118; 95% CI: 0.05 to 0.19; q = 0.006), lower global CT (ß = −0.104; 95% CI: −0.17 to −0.04; q = 0.014), but not WMH volume. Sensitivity analysis revealed no substantial changes after excluding participants with cancer, depression, or hemolysis. Discussion Elevated spermidine plasma levels are associated with advanced brain aging and might serve as potential early biomarker for AD and vascular brain pathology.