Metabolomics: a novel approach to identify potential diagnostic biomarkers and pathogenesis in Alzheimer’s disease

Xu, Xu‐Hua; Huang, Yue; Wang, Gang; Chen, Shengdi

doi:10.1007/s12264-012-1272-0

Cited by 52 publications

(31 citation statements)

References 48 publications

(58 reference statements)

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“…Considering the relatively low analytical reproducibility of capillary electrophoresis [11], we randomly enrolled two independent sets of samples for exploration and replication. The participants were recruited from April 2010 to July 2012 at the outpatient clinic of The University of Tokyo Hospital.…”

Section: Methodsmentioning

confidence: 99%

Altered Metabolites in the Plasma of Autism Spectrum Disorder: A Capillary Electrophoresis Time-of-Flight Mass Spectroscopy Study

et al. 2013

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Clinical diagnosis and severity of autism spectrum disorders (ASD) are determined by trained clinicians based on clinical evaluations of observed behaviors. As such, this approach is inevitably dependent on the expertise and subjective assessment of those administering the clinical evaluations. There is a need to identify objective biological markers associated with diagnosis or clinical severity of the disorder. To identify novel candidate metabolites as potential biomarkers for ASD, the current study applied capillary electrophoresis time-of-flight mass spectroscopy (CE-TOFMS) for high-throughput profiling of metabolite levels in the plasma of 25 psychotropic-naïve adult males with high-functioning ASD and 28 age-matched typically-developed control subjects. Ten ASD participants and ten age-matched controls were assigned in the first exploration set, while 15 ASD participants and 18 controls were included in the second replication set. By CE-TOFMS analysis, a total of 143 metabolites were detected in the plasma of the first set. Of these, 17 metabolites showed significantly different relative areas between the ASD participants and the controls (p<0.05). Of the 17 metabolites, we consistently found that the ASD participants had significantly high plasma levels of arginine (p = 0.024) and taurine (p = 0.018), and significantly low levels of 5-oxoproline (p<0.001) and lactic acid (p = 0.031) compared with the controls in the second sample set. Further confirmatory analysis using quantification of absolute metabolite concentrations supported the robustness of high arginine (p = 0.001) and low lactic acid (p = 0.003) in the combined sample (n = 53). The present study identified deviated plasma metabolite levels associated with oxidative stress and mitochondrial dysfunction in individuals with ASD.

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Section: Methodsmentioning

confidence: 99%

Altered Metabolites in the Plasma of Autism Spectrum Disorder: A Capillary Electrophoresis Time-of-Flight Mass Spectroscopy Study

et al. 2013

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“…A reliable earlystage disease diagnosis tool can also help to position drug interventions at the right temporal therapeutic window for effective detection of treatment effects in AD drug trials [7]. Therefore, tools that allow investigation of the early-stage AD would prove to be invaluable, and metabolic profiling presents itself as a promising approach [8]. Defined as "the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification" [9], metabolic profiling approach offers a distinct advantage over other "-omics" approaches.…”

Section: Introductionmentioning

confidence: 99%

Metabolic Profiling of CHO-AβPP695 Cells Revealed Mitochondrial Dysfunction Prior to Amyloid-β Pathology and Potential Therapeutic Effects of Both PPARγ and PPARα Agonisms for Alzheimer's Disease

Chang

Pee

Tan

et al. 2015

JAD

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In this study, we performed gas chromatography time-of-flight mass spectrometry (GC-TOFMS)-based extracellular metabolic profiling on AβPP-transfected CHO cells (CHO-AβPP695) and its wildtype. Orthogonal partial least squares discriminant analysis (OPLS-DA) was then used to identify discriminant metabolites, which gave clues on the effects of AβPP transgene on cellular processes. To confirm the hypotheses generated based on the metabolic data, we performed biochemical assays to gather further evidence to support our findings. The OPLS-DA showed a robust differentiation following 24 h of incubation (Q2(cum) = 0.884) and 15 discriminant metabolites were identified. In contrast, extracellular Aβ42 was identified to increase significantly in CHO-AβPP695 only after incubation for 48 h. The observed 24-h metabolic fluxes were associated with increased mitochondrial AβPP and reduced mitochondrial viabilities, which occurred before extracellular Aβ accumulation. We also investigated the therapeutic potential of peroxisome proliferator-activated receptor gamma (PPARγ) agonists, namely rosiglitazone (RSG) and pioglitazone (PIO), by employing the same approach to characterize the metabolic profiles of CHO-AβPP695 treated with RSG and PIO, with or without their respective receptor blockers. Treatment with PIO was found to reduce the perturbation of the discriminant metabolites in CHO-AβPP695 to a larger extent than treatment with RSG. We also attributed the PIO effects on the lowering of Aβ42, and restoration of mitochondrial activity to PPARγ and PPARα agonism, respectively. Taken together, PIO was demonstrated to be therapeutically superior to RSG. Our findings provide further insights into early disease stages in this AβPP model, and support the advancement of PIO in AD therapy.

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“…Thus, it is important to have an early and accurate diagnosis of dementia to exclude other types of problems that can lead to cognitive impairment, such as depression, anxiety and sleep disorders and subsequently to choose the appropriate therapy. Early diagnosis can take advantage of biomarkers that may likewise aid the prognosis and assist in controlling the medication's side effects [7][8][9]. AD biomarkers are important for early diagnosis; the core CSF (Cerebrospinal Fluid) biomarkers of neurodegeneration (T-tau, P-tau and Aβ42), CSF NFL and plasma T-tau were strongly associated with AD and associated with mild cognitive impairment.…”

Section: Introductionmentioning

confidence: 99%

FTIR Spectroscopy - A Potential Tool to Identify Metabolic Changes in Dementia Patients

Nunes¹

2016

AND

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Alzheimer's Disease (AD) diagnosis frequently relies on patient's cognitive evaluation deficits and exclusion criteria often implemented in advanced stages of dementia, when it is too late for effective therapeutic intervention. In order to improve early AD diagnosis and therapeutic interventions, novel approaches for AD biomarker identification and validation need to be developed. These comprise metabolomics based strategies, including Fourier Transform Infrared Spectroscopy (FTIR) that has gained increasing attention in the clinical diagnostics field. The present work aims to contribute to identify the main metabolic changes that occur during neurodegeneration, by monitoring plasma biochemical alterations that can aid in dementia/cognitive impairment diagnosis, through FTIR analysis. Principal Component Analysis (PCA) was applied to spectral data (45 plasma samples) at 3 specific regions: 3500-2700 cm-1 , 1700-1400 cm-1 and 1200-900 cm-1. Plasma samples from cognitive impaired individuals exhibit the presence of higher content of saturated lipids, carboxylic acids, reactive carbonyls, and other molecules related to oxidative stress (ROS and NOS species), and protein modifications. Taken together the data obtained in this preliminary work strongly supports that FTIR has potential in diagnosing cognitive impairment, identification of disease states and may prove to also be of prognostic value.

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Metabolomics: a novel approach to identify potential diagnostic biomarkers and pathogenesis in Alzheimer’s disease

Cited by 52 publications

References 48 publications

Altered Metabolites in the Plasma of Autism Spectrum Disorder: A Capillary Electrophoresis Time-of-Flight Mass Spectroscopy Study

Altered Metabolites in the Plasma of Autism Spectrum Disorder: A Capillary Electrophoresis Time-of-Flight Mass Spectroscopy Study

Metabolic Profiling of CHO-AβPP695 Cells Revealed Mitochondrial Dysfunction Prior to Amyloid-β Pathology and Potential Therapeutic Effects of Both PPARγ and PPARα Agonisms for Alzheimer's Disease

FTIR Spectroscopy - A Potential Tool to Identify Metabolic Changes in Dementia Patients

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