title: CSF YKL-40 and pTau181 are related to different cerebral morphometric patterns in early AD.
abstract: Cerebrospinal fluid (CSF) concentrations of YKL-40 that serve as biomarker of neuroinflammation are known to be altered along the clinico-biological continuum of Alzheimer's disease (AD). The specific structural cerebral correlates of CSF YKL-40 were evaluated across the early stages of AD from normal to preclinical to mild dementia. Nonlinear gray matter (GM) volume associations with CSF YKL-40 levels were assessed in a total of 116 subjects, including normal controls and those with preclinical AD as defined by CSF Aβ < 500 pg/mL, mild cognitive impairment (MCI) due to AD, or mild AD dementia. Age-corrected YKL-40 levels were increased in MCIs versus the rest of groups and showed an inverse u-shaped association with p-tau values. A similar nonlinear relationship was found between GM volume and YKL-40 in inferior and lateral temporal regions spreading to the supramarginal gyrus, insula, inferior frontal cortex, and cerebellum in MCI and AD. These findings for YKL-40 remained unchanged after adjusting for p-tau, which was found to be associated with GM volumes in distinct anatomic areas. CSF YKL-40, a biomarker of glial inflammation, is associated with a cerebral structural signature distinct from that related to p-tau neurodegeneration at the earliest stages of cognitive decline due to AD.
authors.affiliation: Clinical and Neuroimaging Departments, Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Spain.
authors.forename: Juan Domingo
authors.initials: JD
authors.lastname: Gispert
authors.affiliation: Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
authors.forename: Gemma C
authors.initials: GC
authors.lastname: Monté
authors.affiliation: Clinical and Neuroimaging Departments, Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Spain.
authors.forename: Carles
authors.initials: C
authors.lastname: Falcon
authors.affiliation: Clinical and Neuroimaging Departments, Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain.
authors.forename: Alan
authors.initials: A
authors.lastname: Tucholka
authors.affiliation: Clinical and Neuroimaging Departments, Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Rojas
authors.affiliation: Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Sánchez-Valle
authors.affiliation: Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Antonell
authors.affiliation: Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Lladó
authors.affiliation: Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Rami
authors.affiliation: Clinical and Neuroimaging Departments, 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. Electronic address: jlmoli@clinic.ub.es.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Molinuevo
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001253:Astrocytes / Q000473:pathology; D015415:Biomarkers / Q000134:cerebrospinal fluid; D000071451:Chitinase-3-Like Protein 1 / Q000134:cerebrospinal fluid*; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000473:pathology; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009457:Neuroglia / Q000473:pathology; D059906:Neuroimaging; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D016875:tau Proteins
keywords: Astrocyte; Astrocytosis; Astroglia; Astrogliosis; Glia; Magnetic resonance imaging (MRI); Microglia; Microgliosis; Neuroimaging; Neuroinflammation; Tau; Voxel-based morphometry (VBM)