posted on 2020-03-11, 20:43authored byAlessia Vignoli, Silvia Paciotti, Leonardo Tenori, Paolo Eusebi, Leonardo Biscetti, Davide Chiasserini, Philip Scheltens, Paola Turano, Charlotte Teunissen, Claudio Luchinat, Lucilla Parnetti
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.