CSF YKL-40 and pTau181 are related to different cerebral morphometric patterns in early AD.

Journal: Neurobiology of aging
PMID:

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

  • Juan Domingo Gispert
    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.
  • Gemma C Monté
    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.
  • Carles Falcon
    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.
  • Alan Tucholka
    Clinical and Neuroimaging Departments, Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain.
  • Santiago Rojas
    Clinical and Neuroimaging Departments, Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain.
  • Raquel Sánchez-Valle
    Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
  • Anna Antonell
    Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
  • Albert Lladó
    Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
  • Lorena Rami
    Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
  • José Luis Molinuevo
    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.