TheAPOEε4 genotype modulates CSF YKL-40 levels and their structural brain correlates in the continuum of Alzheimer's disease but not those of sTREM2.
BACKGROUND
Among other metabolic functions, the apolipoprotein E (APOE) plays a crucial role in neuroinflammation. We aimed at assessing whetherAPOEε4 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 toAPOEε4 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 ε4 status. No similar effects could be detected for sTREM2 levels.


CONCLUSIONS
Our findings are indicative of an increased astroglial activation inAPOEε4 carriers while both groups displayed similar levels of CSF AD core biomarkers.
Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Spain; Pompeu Fabra University, Barcelona, Spain.
Juan Domingo
JD
Gispert
Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Gemma C
GC
Monté
BioMedical Center (BMC), Biochemistry, Ludwig-Maximilians-University Munich, Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, Germany.
Marc
M
Suárez-Calvet
Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Spain.
Carles
C
Falcon
Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain.
Alan
A
Tucholka
Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain; Unit of human Anatomy and Embryology, Department of Morphological Sciences, Faculty of Medicine, Autonomous University of Barcelona, Cerdanyola del Vallès, Spain.
Santiago
S
Rojas
Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Lorena
L
Rami
Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Raquel
R
Sánchez-Valle
Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Albert
A
Lladó
BioMedical Center (BMC), Biochemistry, Ludwig-Maximilians-University Munich, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
Gernot
G
Kleinberger
BioMedical Center (BMC), Biochemistry, Ludwig-Maximilians-University Munich, Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
Christian
C
Haass
Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain; Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
José Luis
JL
Molinuevo
Astrogliosis; Glial biomarkers; Inflammation; Microgliosis; TREM2