Novel insight in idiopathic normal pressure hydrocephalus (Inph) biomarker discovery in csf

Enrica Torretta, Beatrice Arosio, Pietro Barbacini, Daniele Capitanio, Paolo Dionigi Rossi, Manuela Moriggi, Mario Clerici, Daniela Mari, Matteo Cesari, Cecilia Gelfi

Research output: Contribution to journalArticlepeer-review


Idiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible neurological disease, causing motor and cognitive dysfunction and dementia. iNPH and Alzheimer’s disease (AD) share similar molecular characteristics, including amyloid deposition, t-tau and p-tau dysregulation; however, the disease is under-diagnosed and under-treated. The aim was to identify a panel of sphingolipids and proteins in CSF to diagnose iNPH at onset compared to aged subjects with cognitive integrity (C) and AD patients by adopting multiple reaction monitoring mass spectrometry (MRM-MS) for sphingolipid quantitative assessment and advanced high-resolution liquid chromatography–tandem mass spectrometry (LC–MS/MS) for proteomic analysis. The results indicated that iNPH are characterized by an increase in very long chains Cer C22:0, Cer C24:0 and Cer C24:1 and of acute-phase proteins, immunoglobulins and complement component fragments. Proteins involved in synaptic signaling, axogenesis, including BACE1, APP, SEZ6L and SEZ6L2; secretory proteins (CHGA, SCG3 and VGF); glycosylation proteins (POMGNT1 and DAG1); and proteins involved in lipid metabolism (APOH and LCAT) were statistically lower in iNPH. In conclusion, at the disease onset, several factors contribute to maintaining cell homeostasis, and the protective role of very long chains sphingolipids counteract overexpression of amyloidogenic and neurotoxic proteins. Monitoring specific very long chain Cers will improve the early diagnosis and can promote patient follow-up.

Original languageEnglish
Article number8034
JournalInternational Journal of Molecular Sciences
Issue number15
Publication statusPublished - Aug 1 2021


  • Csf
  • Idiopathic normal pressure hydrocephalus
  • Mass spectrometry
  • Proteome
  • Sphingolipids

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


Dive into the research topics of 'Novel insight in idiopathic normal pressure hydrocephalus (Inph) biomarker discovery in csf'. Together they form a unique fingerprint.

Cite this