title: Alzheimer CSF biomarkers may be misleading in normal-pressure hydrocephalus.
abstract: OBJECTIVE
  This article discusses why CSF biomarkers found in normal-pressure hydrocephalus (NPH) can be misleading when distinguishing NPH from comorbid NPH with Alzheimer disease (AD).
  
  
  METHODS
  We describe NPH CSF biomarkers and how shunt surgery can change them. We hypothesize the effects that hydrocephalus may play on interstitial fluid space and amyloid precursor protein (APP) fragment drainage into the CSF based on a recent report and how this may explain the misleading CSF NPH biomarker findings.
  
  
  RESULTS
  In NPH, β-amyloid protein 42 (Aβ42) is low (as in AD), but total tau (t-tau) and phospho-tau (p-tau) levels are normal, providing conflicting biomarker findings. Low Aβ42 supports an AD diagnosis but tau findings do not. Importantly, not only Aβ42, but all APP fragments and tau proteins are low in NPH CSF. Further, these proteins increase after shunting. An increase in interstitial space and APP fragment drainage into the CSF during sleep was reported recently.
  
  
  CONCLUSIONS
  In the setting of hydrocephalus when the brain is compressed, a decrease in interstitial space and APP protein fragment drainage into the CSF may be impeded, resulting in low levels of all APP fragments and tau proteins, which has been reported. Shunting, which decompresses the brain, would create more room for the interstitial space to increase and protein waste fragments to drain into the CSF. In fact, CSF proteins increase after shunting. CSF biomarkers in pre-shunt NPH have low Aβ42 and tau protein levels, providing misleading information to distinguish NPH from comorbid NPH plus AD.
authors.affiliation: From the Department of Neurology, Mayo Clinic, Jacksonville, FL. graffradford.neill@mayo.edu.
authors.forename: Neill R
authors.initials: NR
authors.lastname: Graff-Radford
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D006801:Humans; D006850:Hydrocephalus, Normal Pressure / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins