Fingerprinting Alzheimer's Disease by 1H Nuclear Magnetic Resonance Spectroscopy of Cerebrospinal Fluid

Alessia Vignoli, Silvia Paciotti, Leonardo Tenori, Paolo Eusebi, Leonardo Biscetti, Davide Chiasserini, Philip Scheltens, Paola Turano, Charlotte Teunissen, Claudio Luchinat, Lucilla Parnetti

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In this study, we sought for a cerebrospinal fluid (CSF) metabolomic fingerprint in Alzheimer's disease (AD) patients characterized, according to the clinical picture and CSF AD core biomarkers (Aβ42, p-tau, and t-tau), both at pre-dementia (mild cognitive impairment due to AD, MCI-AD) and dementia stages (ADdem) and in a group of patients with a normal CSF biomarker profile (non-AD) using untargeted 1H nuclear magnetic resonance (NMR) spectroscopy-based metabolomics. This is a retrospective study based on two independent cohorts: a Dutch cohort, which comprises 20 ADdem, 20 MCI-AD, and 20 non-AD patients, and an Italian cohort, constituted by 14 ADdem and 12 non-AD patients. 1H NMR CSF spectra were analyzed using OPLS-DA. Metabolomic fingerprinting in the Dutch cohort provides a significant discrimination (86.1% accuracy) between ADdem and non-AD. MCI-AD patients show a good discrimination with respect to ADdem (70.0% accuracy) but only slight differences when compared with non-AD (59.6% accuracy). Acetate, valine, and 3-hydroxyisovalerate result to be altered in ADdem patients. Valine correlates with cognitive decline at follow-up (R = 0.53, P = 0.0011). The discrimination between ADdem and non-AD was confirmed in the Italian cohort. The CSF metabolomic fingerprinting shows a signature characteristic of ADdem patients with respect to MCI-AD and non-AD patients.

Original languageEnglish
Pages (from-to)1696-1705
Number of pages10
JournalJournal of proteome research
Issue number4
Publication statusPublished - 3 Apr 2020


  • Alzheimer's disease
  • cerebrospinal fluid
  • metabolomics
  • nuclear magnetic resonance
  • total tau and phosphorylated tau

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