PLoS ONE (Jan 2014)

Cerebrospinal fluid biomarker and brain biopsy findings in idiopathic normal pressure hydrocephalus.

  • Okko T Pyykkö,
  • Miikka Lumela,
  • Jaana Rummukainen,
  • Ossi Nerg,
  • Toni T Seppälä,
  • Sanna-Kaisa Herukka,
  • Anne M Koivisto,
  • Irina Alafuzoff,
  • Lakshman Puli,
  • Sakari Savolainen,
  • Hilkka Soininen,
  • Juha E Jääskeläinen,
  • Mikko Hiltunen,
  • Henrik Zetterberg,
  • Ville Leinonen

DOI
https://doi.org/10.1371/journal.pone.0091974
Journal volume & issue
Vol. 9, no. 3
p. e91974

Abstract

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BackgroundThe significance of amyloid precursor protein (APP) and neuroinflammation in idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer's disease (AD) is unknown.ObjectiveTo investigate the role of soluble APP (sAPP) and amyloid beta (Aβ) isoforms, proinflammatory cytokines, and biomarkers of neuronal damage in the cerebrospinal fluid (CSF) in relation to brain biopsy Aβ and hyperphosphorylated tau (HPτ) findings.MethodsThe study population comprised 102 patients with possible NPH with cortical brain biopsies, ventricular and lumbar CSF samples, and DNA available. The final clinical diagnoses were: 53 iNPH (91% shunt-responders), 26 AD (10 mixed iNPH+AD), and 23 others. Biopsy samples were immunostained against Aβ and HPτ. CSF levels of AD-related biomarkers (Aβ42, p-tau, total tau), non-AD-related Aβ isoforms (Aβ38, Aβ40), sAPP isoforms (sAPPα, sAPPβ), proinflammatory cytokines (several interleukins (IL), interferon-gamma, monocyte chemoattractant protein-1, tumor necrosis factor-alpha) and biomarkers of neuronal damage (neurofilament light and myelin basic protein) were measured. All patients were genotyped for APOE.ResultsLumbar CSF levels of sAPPα were lower (pConclusionsThe role of sAPP isoforms in iNPH seems to be independent from the amyloid cascade. No neuroinflammatory background was observed in iNPH or AD.