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Particular CSF sphingolipid patterns identify iNPH and AD patients.

Enrica Torretta1, Beatrice Arosio2,3, Pietro Barbacini1

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Scientific Reports
|September 13, 2018
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Summary

New markers in cerebrospinal fluid (CSF) can help differentiate idiopathic normal pressure hydrocephalus (iNPH) from Alzheimer's disease (AD). Sphingolipid analysis reveals distinct profiles aiding early diagnosis and treatment strategies.

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Medical Diagnostics

Background:

  • Idiopathic normal pressure hydrocephalus (iNPH) presents with reversible neurological symptoms, often mimicking Alzheimer's disease (AD), complicating differential diagnosis.
  • Impaired cerebrospinal fluid (CSF) clearance is a hallmark of iNPH, leading to cognitive decline and necessitating novel diagnostic markers.
  • Distinguishing iNPH from AD is crucial for timely and appropriate therapeutic interventions.

Purpose of the Study:

  • To identify novel biomarkers in serum and CSF for the differential diagnosis of iNPH and AD.
  • To analyze the composition of sphingolipids (SLs) in iNPH and AD patients compared to healthy controls.
  • To explore the potential of specific SLs in improving early diagnostic accuracy and guiding treatment strategies.

Main Methods:

  • Serum SLs analyzed using single-phase extraction and high-performance thin-layer chromatography (HPTLC) with primuline-profiling.
  • CSF SLs analyzed by MALDI profiling and liquid chromatography-mass spectrometry (LC-MS).
  • Comparative analysis of SL profiles across iNPH patients, AD patients, and healthy controls.

Main Results:

  • CSF MALDI profiling showed significantly decreased sphingomyelin C24:1 (SM C24:1) in AD patients compared to iNPH and controls.
  • CSF MALDI profiling indicated increased phosphatidylcholine 36:2 (PC 36:2) in iNPH patients.
  • CSF LC-MS revealed a decrease in sphingosine-1-phosphate (S1P) and an increase in glucosylceramide C24:0 (GlcCer C24:0) in AD compared to iNPH patients.

Conclusions:

  • CSF PC 36:2 and SM C24:1 levels can aid in differentiating iNPH from AD.
  • CSF S1P and GlcCer C24:0 levels show potential as markers for distinguishing AD from iNPH.
  • These CSF sphingolipid markers may enhance differential diagnosis, enabling earlier therapeutic strategies for iNPH and AD.