In this study we sought for a cerebrospinal fluid (CSF) metabolomic fingerprint in Alzheimer's Disease (AD) patients characterized, according to 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 stage (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.
Fingerprinting Alzheimer's Disease by 1H Nuclear Magnetic Resonance Spectroscopy of Cerebrospinal Fluid
Paciotti, Silvia;Eusebi, Paolo;Biscetti, Leonardo;Chiasserini, Davide;Parnetti, Lucilla
2020
Abstract
In this study we sought for a cerebrospinal fluid (CSF) metabolomic fingerprint in Alzheimer's Disease (AD) patients characterized, according to 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 stage (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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
