Bogdanov M, Matson W, Wang L, Matson T, Saunders-Pullman R, Bressman S et al. Metabolomic profiling to develop blood biomarkers for Parkinson's disease. Brain 131: 389-396

Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, 525 East 68th Street, F610, New York, NY 10021, USA.
Brain (Impact Factor: 9.2). 03/2008; 131(Pt 2):389-96. DOI: 10.1093/brain/awm304
Source: PubMed


The development of biomarkers for the diagnosis and monitoring disease progression in Parkinson's disease (PD) is of great importance since diagnosis based on clinical parameters has a considerable error rate. In this study, we utilized metabolomic profiling using high performance liquid chromatography coupled with electrochemical coulometric array detection (LCECA) to look for biomarkers in plasma useful for the diagnosis of PD. We examined 25 controls and 66 PD patients. We also measured 8-hydroxy-2-deoxyguanosine (8-OHdG) levels as a marker of oxidative damage to DNA. We initially examined the profiles of unmedicated PD subjects compared to controls to rule out confounding effects of symptomatic medications. We found a complete separation of the two groups. We then determined the variables, which played the greatest role in separating the two groups and applied them to PD subjects taking dopaminergic medications. Using these parameters, we achieved a complete separation of the PD patients from controls. 8-OHdG levels were significantly increased in PD patients, but overlapped controls. Two other markers of oxidative damage were measured in our LCECA profiles. Uric acid was significantly reduced while glutathione was significantly increased in PD patients. These findings show that metabolomic profiling with LCECA coulometric array has great promise for developing biomarkers for both the diagnosis, as well as monitoring disease progression in PD.

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    • "Metabolomic interest in PD and AD has concentrated on markers of damage (e.g. hypoxia, oxidative stress and membrane lipid remodelling) in blood (Bogdanov et al. 2008; Orešič et al. 2011) and breath (Nakhleh et al. 2015). "
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    ABSTRACT: We seek an aetiopathogenic model for the spectrum of Parkinson's disease (PD), functional bowel disease, depression and cognitive impairment. The adopted concept is that systemic immuno-inflammatory processes mediate neuro-inflammation. The model would be based on phenotype, exposome (including gastrointestinal microbiome), milieu (immuno-inflammatory and metabolome), human genetics and their interactions. It would enable a patient's position, to be understood in terms of drivers, perpetuators and mediators, and a future position, with and without intervention, predicted. Even the cardinal facets of PD may have different drivers: halting one may allow escape down subordinate pathways. Peptic ulceration is prodromal to PD. In our randomised placebo-controlled trial, hypokinesia improved over the year following biopsy-proven Helicobacter pylori eradication and rigidity worsened. This was independent of any (stable, long t½) antiparkinsonian medication. There are pointers to an autoimmune process: for example, surveillance-confirmed hypokinesia effect was indication specific. During surveillance, successive antimicrobial courses, other than for Helicobacter, were associated with cumulative increase in rigidity. Exhibiting laxatives appeared to stem the overall temporal increase, despite antiparkinsonian medication, in rigidity. Thus, intestinal dysbiosis may be a major source of bystander neuronal damage. There are biological gradients of objective measures of PD facets on circulating inflammatory markers and leucocyte subset counts. Moreover, lactulose hydrogen breath test positivity for small-intestinal bacterial overgrowth (present in two thirds of PD patients) is associated with the same subsets: higher natural killer and total CD4+ counts and lower neutrophils. With greater aetiopathogenic understanding, relatively low cost and on-the-shelf medication could have a major impact. A new generation of animal models, based on the gut microbiome, is envisaged.
    Journal of NeuroVirology 06/2015; DOI:10.1007/s13365-015-0357-8 · 2.60 Impact Factor
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    • "Sharma et al. (2013) published a comprehensive review about the recently discovered biomarkers for PD diagnosis which covers clinical, neuroimaging, biochemical, genetic and proteomic biomarkers. However, none of these biomarkers is in routine clinical use, and a need still exists for new early, noninvasive, sensitive, specific and economical peripheral and/or central diagnostic biomarkers for the differential diagnosis, prognosis, and monitoring of treatment success (Ahmed et al., 2009; Bogdanov et al., 2008; Greenberg et al., 2009; Michell et al., 2008; Quinones and Kaddurah-Daouk, 2009). A human disease may have specific biochemical pathways which produce compounds specific to that disease. "
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    ABSTRACT: Parkinson’s disease (PD) is characterized by dopaminergic (DA) neuron depletion. Early detection of PD may help in selecting the appropriate treatment. Biomarkers of PD have been suggested, however none of these is currently in clinical use. The aim of this study was to identify volatile organic compounds (VOCs) as early biomarkers of PD. Our hypothesis was that during PD progression, specific VOCs are generated that are linked to the biochemical pathways characterizing PD. These VOCs can be detected by GC–MS combined with solid-phase microextraction (SPME) technique. Three groups of rats were studied: DA-lesioned rats injected with 6-hydroxydopamine (HDA; 250 μg/rat n=11); control rats injected with saline (n=9), and control rats injected with DSP-4 (n=8), a specific noradrenergic neuron toxin. Blood and striatal tissue homogenate were analyzed. In the blood, 1-octen-3-ol and 2-ethylhexanol were found at significantly higher concentrations in HDA versus sham rats. In the striatal homogenate 1-octen-3-ol and other four compounds were found at significantly lower concentrations in HDA versus sham rats. 1-Octen-3-ol is a cytotoxic compound. These results may lead to the development of an early diagnostic test for PD based on profiling of VOCs in body fluids.
    Neurochemistry International 10/2014; DOI:10.1016/j.neuint.2014.06.016 · 3.09 Impact Factor
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    • "Metabolomics also holds promise for early diagnosis of disease and for identification of metabolic pathways as targets for disease amelioration [13]. Serum metabolomics of CNS disorders has been vindicated by identification of blood biomarkers of Parkinson’s disease [2]. Serum is the basic sample for metabolomics, being readily collectable by minimally invasive techniques, but serum metabolic profiles of responders and non-responders to anti-epilepsy drugs may not be clearly distinguishable [1]. "
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    ABSTRACT: Epilepsy is a common neurological disorder with seizures, but diagnostic approaches in veterinary clinics remain limited. Cerebrospinal fluid (CSF) is a body fluid used for diagnosis in veterinary medicine. In this study, we explored canine epilepsy diagnostic biomarkers using gas chromatography-mass spectrometry (GC-MS)-based metabolic profiling of CSF and multivariate data analysis. Profiles for subjects with idiopathic epilepsy differed significantly from those of healthy controls and subjects with symptomatic epilepsy. Among 60 identified metabolites, the levels of 20 differed significantly among the three groups. Glutamic acid was significantly increased in idiopathic epilepsy, and some metabolites including ascorbic acid were changed in both forms of epilepsy. These findings show that metabolic profiles of CSF differ between idiopathic and symptomatic epilepsy and that metabolites including glutamic acid and ascorbic acid in CSF may be useful for diagnosis of canine epilepsy.
    Journal of Veterinary Medical Science 12/2013; 76(4). DOI:10.1292/jvms.13-0520 · 0.78 Impact Factor
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