The APOE ε4 genotype modulates CSF YKL-40 levels and their structural brain correlates in the continuum of Alzheimer's disease but not those of sTREM2

Abstract Introduction Among other metabolic functions, the apolipoprotein E (APOE) plays a crucial role in neuroinflammation. We aimed at assessing whether APOE e4 modulates levels of glial cerebrospinal fluid (CSF) biomarkers and their structural cerebral correlates along the continuum of Alzheimer's disease (AD). Methods Brain magnetic resonance imaging (MRI) scans were acquired in 110 participants (49 control; 19 preclinical; 27 mild cognitive impairment [MCI] due to AD; 15 mild AD dementia) and CSF concentrations of YKL-40 and sTREM2 were determined. Differences in CSF biomarker concentrations and interactions in their association with gray-matter volume according to APOE e4 status were sought after. Results Preclinical and MCI carriers showed higher YKL-40 levels. There was a significant interaction in the association between YKL-40 levels and gray-matter volume according to e4 status. No similar effects could be detected for sTREM2 levels. Discussion Our findings are indicative of an increased astroglial activation in APOE e4 carriers while both groups displayed similar levels of CSF AD core biomarkers.