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.

Novel insight in idiopathic normal pressure hydrocephalus (iNPH) biomarker discovery in CSF / E. Torretta, B. Arosio, P. Barbacini, D. Capitanio, P.D. Rossi, M. Moriggi, M. Clerici, D. Mari, M. Cesari, C. Gelfi. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 22:15(2021 Jul 27), pp. 8034.1-8034.18. [10.3390/ijms22158034]

Novel insight in idiopathic normal pressure hydrocephalus (iNPH) biomarker discovery in CSF

E. Torretta
Primo
;
B. Arosio;P. Barbacini;D. Capitanio;M. Moriggi;M. Clerici;D. Mari;M. Cesari;C. Gelfi
Ultimo
2021-07-27

Abstract

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.
Csf; idiopathic normal pressure hydrocephalus; mass spectrometry; proteome; sphingolipids
Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
Settore MED/09 - Medicina Interna
Settore BIO/13 - Biologia Applicata
CAR_RIC18CGELF_01 - Increased sarcopenia in a cohort of elderly carrying snap25 polymorphisms: mechanistic insights from the SNAP25 heterozygous murine model - GELFI, CECILIA - CAR_RIC - Bandi Fondazione Cariplo - 2018
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/866736
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