title: CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings.
abstract: OBJECTIVE
  To assess the relationship between Alzheimer disease (AD)-related pathologic changes in frontal cortical brain biopsy and AD biomarkers in ventricular vs lumbar CSF, and to evaluate the relationships of AD biomarkers in CSF and cortical biopsy with the final clinical diagnosis of AD.
  
  
  METHODS
  In 182 patients with presumed normal pressure hydrocephalus (152 with known APOE carrier status), Aβ plaques and tau in the cortical brain biopsies were correlated with the ventricular and lumbar CSF Aβ42, total tau, and p-tau levels measured by ELISA. In a median follow-up of 2.0 years, 51 patients developed AD dementia.
  
  
  RESULTS
  The patients with Aβ plaques in the cortical biopsy had lower (p = 0.009) CSF Aβ42 levels than those with no Aβ plaques. The patients with tau in the cortical biopsy had lower (p = 0.014) Aβ42 but higher (p = 0.015) p-tau 181 in CSF as compared to those with no tau in the cortical biopsy. The patients with amyloid + tau + biopsies had the lowest Aβ42 and highest tau and p-tau 181 levels in CSF. The Aβ42 levels were lower and the tau and p-tau 181 higher in the ventricular vs corresponding lumbar CSF samples. In multivariate analysis, the presence of cortical Aβ was independently predicted by the APOE ε4 carrier status and age but not by CSF Aβ42 or tau levels.
  
  
  CONCLUSIONS
  Amyloid plaques and hyperphosphorylated tau in cortical brain biopsies are reflected by low CSF Aβ42 and high CSF tau and p-tau levels, respectively.
authors.affiliation: Unit of Neurology, Institute of Clinical Medicine, University of Eastern Finland. toni.seppala@fimnet.fi
authors.forename: T T
authors.initials: TT
authors.lastname: Seppälä
authors.forename: O
authors.initials: O
authors.lastname: Nerg
authors.forename: A M
authors.initials: AM
authors.lastname: Koivisto
authors.forename: J
authors.initials: J
authors.lastname: Rummukainen
authors.forename: L
authors.initials: L
authors.lastname: Puli
authors.forename: H
authors.initials: H
authors.lastname: Zetterberg
authors.forename: O T
authors.initials: OT
authors.lastname: Pyykkö
authors.forename: S
authors.initials: S
authors.lastname: Helisalmi
authors.forename: I
authors.initials: I
authors.lastname: Alafuzoff
authors.forename: M
authors.initials: M
authors.lastname: Hiltunen
authors.forename: J E
authors.initials: JE
authors.lastname: Jääskeläinen
authors.forename: J
authors.initials: J
authors.lastname: Rinne
authors.forename: H
authors.initials: H
authors.lastname: Soininen
authors.forename: V
authors.initials: V
authors.lastname: Leinonen
authors.forename: S K
authors.initials: SK
authors.lastname: Herukka
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000235:genetics / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D053327:Apolipoprotein E4; D001706:Biopsy; D016009:Chi-Square Distribution; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005625:Frontal Lobe / Q000473:pathology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D011569:Psychiatric Status Rating Scales; D013223:Statistics as Topic; D018709:Statistics, Nonparametric; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins