Ludwig-Maximilians-Universität, Chair of Metabolic Biochemistry

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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

Alzheimers Dement (Amst). 2016 Dec 22;6:50-59

Authors/Editors: Juan Domingo Gispert
Gemma C. Monté
Marc Suárez-Calvet
Carles Falcon
Alan Tucholka
Santiago Rojas
Lorena Rami
Raquel Sánchez-Valle
Albert Lladó
Gernot Kleinberger
Christian Haass
José Luis Molinuevo
Publication Date: 2016
Type of Publication: Journal Article


Among other metabolic functions, the apolipoprotein E (APOE) plays a crucial role in neuroinflammation. We aimed at assessing whether APOE ε4 modulates levels of glial cerebrospinal fluid (CSF) biomarkers and their structural cerebral correlates along the continuum of Alzheimer's disease (AD).


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 ε4 status were sought after.


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 ε4 status. No similar effects could be detected for sTREM2 levels.


Our findings are indicative of an increased astroglial activation in APOE ε4 carriers while both groups displayed similar levels of CSF AD core biomarkers.

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