title: Cerebrospinal fluid biomarkers for Alzheimer's disease: the role of apolipoprotein E genotype, age, and sex.
abstract: BACKGROUND
  Cerebrospinal fluid (CSF) biomarkers improve the diagnostic accuracy for Alzheimer's disease (AD), even at the predementia stage of the disease. The ε4-allele of apolipoprotein E (ApoE ε4), female sex, and older age are well-known risk factors for AD. It is unclear how these risk factors affect the CSF biomarkers in patients with AD.
  
  
  OBJECTIVE
  The objective of this study was to investigate the associations of ApoE ε4, sex, and age with CSF biomarker levels in a unicenter sample of patients with AD that includes a high proportion of patients with early-onset AD (EOAD).
  
  
  METHODS
  The CSF levels of amyloid-β 1-42 (Aβ1-42) and total-tau of 117 subjects with mild to moderate AD (55 late-onset AD and 62 EOAD) were assessed. All subjects underwent ApoE genotyping, clinical evaluation, comprehensive neuropsychological assessments, and neuroimaging. Associations between CSF biomarker levels, ApoE ε4 allele frequency, age, and sex were evaluated.
  
  
  RESULTS
  In the whole patient sample and in the late-onset AD subgroup ε4 homozygous subjects had significantly lower CSF Aβ1-42 levels compared with ε4 heterozygous subjects and ε4 noncarriers. This association was not detected in the EOAD group. Age group, sex, and severity of cognitive decline did not have a significant impact on CSF Aβ1-42 levels. No significant associations were found between ApoE ε4 allele frequency and CSF total-tau levels.
  
  
  CONCLUSIONS
  ApoE ε4 allele is associated with a reduction of CSF Aβ1-42 levels. This result is consistent with the findings of several previous studies. In the subgroup of patients with EOAD this association was not replicated. Larger studies are necessary to further investigate associations between ApoE ε4 allele frequency and CSF biomarker levels in patients with EOAD.
authors.affiliation: Department of Neurology, University Hospital "Alexandrovska", Sofia, Bulgaria.
authors.forename: Shima
authors.initials: S
authors.lastname: Mehrabian
authors.affiliation: Department of Psychiatry, Technische Universität München, Munich, Germany ; Department of Psychiatry, University of Patras, Patras, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Alexopoulos
authors.affiliation: Department of Psychiatry, Technische Universität München, Munich, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Ortner
authors.affiliation: Department of Neurology, University Hospital "Alexandrovska", Sofia, Bulgaria.
authors.forename: Latchezar
authors.initials: L
authors.lastname: Traykov
authors.affiliation: Department of Psychiatry, Technische Universität München, Munich, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Grimmer
authors.affiliation: Department of Psychiatry, Technische Universität München, Munich, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kurz
authors.affiliation: Department of Psychiatry, Technische Universität München, Munich, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Förstl
authors.affiliation: Department of Psychiatry, Technische Universität München, Munich, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Bickel
authors.affiliation: Department of Psychiatry, Technische Universität München, Munich, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Diehl-Schmid
keywords: Alzheimer’s disease; ApoE; Aβ1-42; CSF; EOAD; LOAD; biomarkers; tau