Soluble amyloid precursor protein α in the cerebrospinal fluid as a diagnostic and prognostic biomarker for idiopathic normal pressure hydrocephalus

Eur J Neurol. 2013 Feb;20(2):236-42. doi: 10.1111/j.1468-1331.2012.03781.x. Epub 2012 Jun 4.


Background: Cognitive impairment is difficult to improve after shunt operation in patients with idiopathic normal pressure hydrocephalus (iNPH). This study aims to identify cerebrospinal fluid (CSF) biomarkers predictive of improvement in cognitive function.

Methods: This study was conducted between January 2008 and December 2010 on consecutive, unselected admissions to our program for the treatment of patients with clinically suspected iNPH. Lumbar CSF concentrations of total tau (Tau), tau phosphorylated at threonine 181 (p-tau), soluble amyloid precursor protein (sAPP), sAPPα, sAPPβ, and β-amyloid(1-42) (Aβ42) were analyzed by ELISA.

Results: Concentrations of p-tau, sAPP, sAPPα, and sAPPβ were strong diagnostic biomarkers for distinguishing between iNPH and Alzheimer's disease (AD). sAPPα exhibited the highest accuracy in differentiating iNPH from patients with AD and normal controls, with an area under the curve value of 0.994. We examined the prognostic value of p-tau and sAPPα for cognition function after surgery. With a cutoff value of 198 ng/ml or less for sAPPα, sensitivity and specificity are 66.7% and 82.9%, respectively, whilst the Mini-Mental State Examination score at 6 months after surgery is expected to be 25 or more.

Conclusion: Our results show that sAPPα is a suitable biomarker for the diagnosis and prognosis of iNPH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / diagnosis
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / cerebrospinal fluid*
  • Amyloid beta-Protein Precursor / metabolism
  • Biomarkers / cerebrospinal fluid
  • Biomarkers / metabolism
  • Female
  • Humans
  • Hydrocephalus, Normal Pressure / cerebrospinal fluid*
  • Hydrocephalus, Normal Pressure / diagnosis*
  • Male
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid
  • Peptide Fragments / metabolism
  • Prognosis
  • Sensitivity and Specificity
  • Solubility
  • tau Proteins / cerebrospinal fluid
  • tau Proteins / metabolism


  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Biomarkers
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins