Biomarkers in amyotrophic lateral sclerosis: combining metabolomic and clinical parameters to define disease progression

Blasco, Hélène; Nadal-Desbarats, Lydie; Pradat, Pierre; Gordon, Paul H.; Hounoum, Blandine Madji; Patin, Franck; Veyrat-Durebex, Charlotte; Mavel, Sylvie; Beltran, S.; Emond, Patrick; Andres, Christian R.; Corcia, P.

doi:10.1111/ene.12851

Cited by 20 publications

(18 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Greater expression of total or cytoplasmic TDP-43, which occurs in bulbar onset ALS and ALS associated with FTD, is correlated with poorer prognosis, meaning shorter survival time from diagnosis or shorter time elapsed to indication of mechanical ventilation. This idea is in line with studies suggesting that the measurement of TDP-43 may be a prognostic biomarker of the disease (70), although several other studies show elevations in CSF cannot be considered a sensitive diagnostic marker at that moment (71, 72). …”

Section: Discussionsupporting

confidence: 84%

Immununochemical Markers of the Amyloid Cascade in the Hippocampus in Motor Neuron Diseases

et al. 2016

View full text Add to dashboard Cite

BackgroundSeveral findings suggest that the amyloid precursor protein (APP) and the amyloid cascade may play a role in motor neuron disease (MND).ObjectiveConsidering that dementia is one of the most frequent non-motor symptoms in amyotrophic lateral sclerosis (ALS) and that hippocampus is one of the brain areas with greater presence of amyloid-related changes in neurodegenerative diseases, our aim was to analyze the molecular markers of the amyloid cascade of APP in pathology studies of the hippocampus of autopsied patients with ALS and ALS–frontotemporal dementia (FTD).MethodsWe included nine patients with MND and four controls. Immunohistochemical studies and confocal microscopy were used to analyze the expression of APP, TDP-43, pho-TDP-43, Aβ, APP intracellular cytoplasmatic domain (AICD) peptide, Fe65 protein, and pho-TAU in the hippocampus of seven patients with ALS, two patients with ALS–FTD, and four controls. These findings were correlated with clinical data.ResultsPatients displayed increased expression of APP and Aβ peptide. The latter was correlated with cytoplasmic pho-TDP-43 expression. We also found decreased Fe65 expression. A parallel increase in AICD expression was not found. Patients showed increased expression of pho-TAU in the hippocampus. Findings were similar in patients with ALS and those with ALS–FTD, though more marked in the latter group.ConclusionPost-mortem analyses showed that the amyloid cascade is activated in the hippocampus of patients with MND and correlated with cytoplasmic pho-TDP-43 expression. The number of intracellular or extracellular aggregates of Aβ peptides was not significant.

show abstract

Section: Discussionsupporting

confidence: 84%

Immununochemical Markers of the Amyloid Cascade in the Hippocampus in Motor Neuron Diseases

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Among those, amine and lactate, as well as the amino acids, phenylalanine and tyrosine, glucose, acetone, and inositol were determined in CSF of ALS patients (Blasco et al, 2015;Gray et al, 2015;Toczylowska et al, 2013). Besides CSF and plasma, lactate was determined in serum of patients having ALS disease (Botosoa et al, 2012;Lawton et al, 2014).…”

Section: Resultsmentioning

confidence: 99%

“…In addition, low levels of alkaloids (caffeine, paraxanthine, theobromine, and theophylline), and hippurate were observed in ALS patients (Blasco et al, 2015;Botosoa et al, 2012;Gray et al, 2015;Kumar et al, 2010;Lawton et al, 2012Lawton et al, , 2014Toczylowska et al, 2013;Zoccolella et al, 2008).…”

Section: Resultsmentioning

confidence: 99%

“…The choline, Lglutamine, and alanine levels were increased in AD and ALS, but they were decreased in PD. The creatine and creatinine levels were also increased in AD and decreased in PD, but their expression patterns in ALS were not stable and fluid dependent (Abraham and Drory, 2014;Ahmed et al, 2009;Blasco et al, 2015;Botosoa et al, 2012;Cui et al, 2014;González-Domínguez et al, 2014a;Gröger et al, 2014;Jukarainen et al, 2008;Kantarci et al, 2000;Kim et al, 2006;Kumar et al, 2010;Lawton et al, 2012;Toczylowska et al, 2013;Trupp et al, 2014;Trushina and Mielke, 2014;Wuolikainen et al, 2011).…”

Section: Fig 1 Distribution Of Metabolic Biomarkers In Biochemical mentioning

confidence: 99%

“…Phenotypic heterogeneity and lack of diagnostic biomarkers pose difficulties in establishing the diagnosis in very early stages. Indeed, the interval time between the appearance of first symptoms and the diagnosis is more than 1 year and often, it is greater (Blasco et al, 2015(Blasco et al, , 2016.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Metabolic Biomarkers and Neurodegeneration: A Pathway Enrichment Analysis of Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis

Kori

Aydın

Unal

et al. 2016

OMICS: A Journal of Integrative Biology

125

View full text Add to dashboard Cite

Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) lack robust diagnostics and prognostic biomarkers. Metabolomics is a postgenomics field that offers fresh insights for biomarkers of common complex as well as rare diseases. Using data on metabolite-disease associations published in the previous decade (2006-2016) in PubMed, ScienceDirect, Scopus, and Web of Science, we identified 101 metabolites as putative biomarkers for these three neurodegenerative diseases. Notably, uric acid, choline, creatine, L-glutamine, alanine, creatinine, and N-acetyl-L-aspartate were the shared metabolite signatures among the three diseases. The disease-metabolite-pathway associations pointed out the importance of membrane transport (through ATP binding cassette transporters), particularly of arginine and proline amino acids in all three neurodegenerative diseases. When disease-specific and common metabolic pathways were queried by using the pathway enrichment analyses, we found that alanine, aspartate, glutamate, and purine metabolism might act as alternative pathways to overcome inadequate glucose supply and energy crisis in neurodegeneration. These observations underscore the importance of metabolite-based biomarker research in deciphering the elusive pathophysiology of neurodegenerative diseases. Future research investments in metabolomics of complex diseases might provide new insights on AD, PD, and ALS that continue to place a significant burden on global health.

show abstract

Advanced Statistical Methods for NMR-Based Metabolomics

Zhang

2019

NMR-Based Metabolomics

View full text Add to dashboard Cite

Biomarkers in amyotrophic lateral sclerosis: combining metabolomic and clinical parameters to define disease progression

Cited by 20 publications

References 34 publications

Immununochemical Markers of the Amyloid Cascade in the Hippocampus in Motor Neuron Diseases

Immununochemical Markers of the Amyloid Cascade in the Hippocampus in Motor Neuron Diseases

Metabolic Biomarkers and Neurodegeneration: A Pathway Enrichment Analysis of Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis

Advanced Statistical Methods for NMR-Based Metabolomics

Contact Info

Product

Resources

About