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  • 1.
    Figueira, Joao
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Jonsson, Pär
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Nordin Adolfsson, Annelie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Öhman, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    NMR analysis of the human saliva metabolome distinguishes dementia patients from matched controls2016In: Molecular Biosystems, ISSN 1742-206X, E-ISSN 1742-2051, Vol. 12, no 8, p. 2562-2571Article in journal (Refereed)
    Abstract [en]

    Saliva is a biofluid that is sensitive to metabolic changes and is straightforward to collect in a non-invasive manner, but it is seldom used for metabolite analysis when studying neurodegenerative disorders. We present a procedure for both an untargeted and targeted analysis of the saliva metabolome in which nuclear magnetic resonance (NMR) spectroscopy is used in combination with multivariate data analysis. The applicability of this approach is demonstrated on saliva samples selected from the 25 year prospective Betula study, including samples from dementia subjects with either Alzheimer's disease (AD) or vascular dementia at the time of sampling or who developed it by the next sampling/assessment occasion five years later, and age-, gender-, and education-matched control individuals without dementia. Statistically significant multivariate models were obtained that separated patients with dementia from controls and revealed seven discriminatory metabolites. Dementia patients showed significantly increased concentrations of acetic acid (fold change (fc) = 1.25, p = 2 x 10(-5)), histamine (fc = 1.26, p = 0.019), and propionate (fc = 1.35, p = 0.002), while significantly decreased levels were observed for dimethyl sulfone (fc = 0.81, p = 0.005), glycerol (fc = 0.79, p = 0.04), taurine (fc = 0.70, p = 0.007), and succinate (fc = 0.62, p = 0.008). Histamine, succinate, and taurine are known to be important in AD, and acetic acid and glycerol are involved in related pathways. Dimethyl sulfone and propionate originate from the diet and bacterial flora and might reflect poorer periodontal status in the dementia patients. For these seven metabolites, a weak but statistically significant pre-diagnostic value was observed. Taken together, we present a robust and general NMR analysis approach for studying the saliva metabolome that has potential use for screening and early detection of dementia.

  • 2. Pohjoismäki, Jaakko L O
    et al.
    Krüger, Marcus
    Al-Furoukh, Natalie
    Department of Cardiac Development and Remodelling, Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany.
    Lagerstedt, Anssi
    Karhunen, Pekka J
    Braun, Thomas
    Postnatal cardiomyocyte growth and mitochondrial reorganization cause multiple changes in the proteome of human cardiomyocytes.2013In: Molecular Biosystems, ISSN 1742-206X, E-ISSN 1742-2051, Vol. 9, no 6Article in journal (Refereed)
    Abstract [en]

    Fetal (fCM) and adult cardiomyocytes (aCM) significantly differ from each other both by structure and biochemical properties. aCM own a higher mitochondrial mass compared to fCM due to increased energy demand and show a greater density and higher degree of structural organization of myofibrils. The energy metabolism in aCM relies virtually completely on β-oxidation of fatty acids while fCM use carbohydrates. Rewinding of the aCM phenotype (de-differentiation) arises frequently in diseased hearts spurring questions about its functional relevance and the extent of de-differentiation. Yet, surprisingly little is known about the changes in the human proteome occurring during maturation of fCM to aCM. Here, we examined differences between human fetal and adult hearts resulting in the quantification of 3500 proteins. Moreover, we analyzed mitochondrial proteomes from both stages to obtain more detailed insight into underlying biochemical differences. We found that the majority of changes between fCM and aCM were attributed to growth and maturation of cardiomyocytes. As expected, adult hearts showed higher mitochondrial mass and expressed increased levels of proteins involved in energy metabolism but relatively lower copy numbers of mitochondrial DNA (mtDNA) per total cell volume. We uncovered that the TFAM/mtDNA ratio was kept constant during postnatal development despite a significant increase of mitochondrial protein per mtDNA in adult mitochondria, which revises previous concepts.

  • 3.
    Wuolikainen, Anna
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Jonsson, Pär
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Ahnlund, Maria
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Marklund, Stefan L.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Moritz, Thomas
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Andersen, Peter M.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Trupp, Miles
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Multi-platform mass spectrometry analysis of the CSF and plasma metabolomes of rigorously matched amyotrophic lateral sclerosis, Parkinson's disease and control subjects2016In: Molecular Biosystems, ISSN 1742-206X, E-ISSN 1742-2051, Vol. 12, no 4, p. 1287-1298Article in journal (Refereed)
    Abstract [en]

    Amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) are protein-aggregation diseases that lack clear molecular etiologies. Biomarkers could aid in diagnosis, prognosis, planning of care, drug target identification and stratification of patients into clinical trials. We sought to characterize shared and unique metabolite perturbations between ALS and PD and matched controls selected from patients with other diagnoses, including differential diagnoses to ALS or PD that visited our clinic for a lumbar puncture. Cerebrospinal fluid (CSF) and plasma from rigorously age-, sex- and sampling-date matched patients were analyzed on multiple platforms using gas chromatography (GC) and liquid chromatography (LC)-mass spectrometry (MS). We applied constrained randomization of run orders and orthogonal partial least squares projection to latent structure-effect projections (OPLS-EP) to capitalize upon the study design. The combined platforms identified 144 CSF and 196 plasma metabolites with diverse molecular properties. Creatine was found to be increased and creatinine decreased in CSF of ALS patients compared to matched controls. Glucose was increased in CSF of ALS patients and alpha-hydroxybutyrate was increased in CSF and plasma of ALS patients compared to matched controls. Leucine, isoleucine and ketoleucine were increased in CSF of both ALS and PD. Together, these studies, in conjunction with earlier studies, suggest alterations in energy utilization pathways and have identified and further validated perturbed metabolites to be used in panels of biomarkers for the diagnosis of ALS and PD.

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