Metabolite Profiling of Alzheimer's Disease Cerebrospinal Fluid

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive loss of cognitive functions. Today the diagnosis of AD relies on clinical evaluations and is only late in the disease. Biomarkers for early detection of the underlying neuropathological changes are still lacking and the biochemical pathways leading to the disease are still not completely understood. The aim of this study was to identify the metabolic changes resulting from the disease phenotype by a thorough and systematic metabolite profiling approach. For this purpose CSF samples from 79 AD patients and 51 healthy controls were analyzed by gas and liquid chromatography-tandem mass spectrometry (GC-MS and LC-MS/MS) in conjunction with univariate and multivariate statistical analyses. In total 343 different analytes have been identified. Significant changes in the metabolite profile of AD patients compared to healthy controls have been identified. Increased cortisol levels seemed to be related to the progression of AD and have been detected in more severe forms of AD. Increased cysteine associated with decreased uridine was the best paired combination to identify light AD (MMSE>22) with specificity and sensitivity above 75%. In this group of patients, sensitivity and specificity above 80% were obtained for several combinations of three to five metabolites, including cortisol and various amino acids, in addition to cysteine and uridine.

Perspective on future role of biological markers in clinical therapy trials of Alzheimer's disease: A long-range point of view beyond 2020

“…One study has showed the increase of the concentrations of eight amino acids in AD versus MCI [111]. Another larger examination, after measuring 343 analytes has also led to detect eight molecules with statistical significance; interestingly, one of these markers, cortisol, correlated with the advancement of the disease [112]. A disadvantage with metabolomics as compared with proteomics and peptidomics may be that, in contrast to several proteins, there is no data showing an established role for small (non-protein) molecules in AD pathogenesis.…”

New Frontiers in Alzheimer's Disease Diagnosis

“…The metabolic profile in human CSF samples of AD patients and agematched healthy controls unveils the presence of a significant presence of deregulated metabolites in AD cases [190]. Among them, higher corticols levels are found in AD cases, which correlate with AD progression and severity.…”

Metabolic Profiling and Phenotyping of Central Nervous System Diseases: Metabolites Bring Insights into Brain Dysfunctions

“…3) indicates convergent variations in these pathways (Czech et al 2012). Importantly, the severity of the disease was correlated with decreased noradrenaline (Kaddurah-Daouk et al 2011b) and increased levels of vanillylmandelic acid, a degradation product of xanthine and dopamine (Kaddurah-Daouk et al 2013b).…”

“…Also, MSEA (Tab. 3) highlighted that two independent studies indicated alterations in methionine metabolism (Czech et al 2012;Ibanez et al 2012).…”