Elevated Glutamate and Glutamine Levels in the Cerebrospinal Fluid of Patients With Probable Alzheimer's Disease and Depression

Madeira, Caroline; Vargas-Lopes, Charles; Brandão, Carlos Otávio; Reis, Taylor; Laks, Jérson; Panizzutti, Rogério; Ferreira, Sérgio T.

doi:10.3389/fpsyt.2018.00561

Cited by 139 publications

(96 citation statements)

References 71 publications

(92 reference statements)

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“…Regarding univariate analysis, glutamine showed negative correlation with MMSE score. Similarly, previous studies showed increased CSF levels of glutamate and glutamine in patients with probable AD 24 . In addition, the glutamate/glutamine ratio showed a reduction in ageing and AD 40 .…”

Section: Discussionsupporting

confidence: 72%

Early neurotransmission impairment in non-invasive Alzheimer Disease detection

Peña-Bautista

Torres-Cuevas

Baquero

et al. 2020

Sci Rep

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Alzheimer Disease (AD) is a pathology suffered by millions of people worldwide and it has a great social and economic impact. Previous studies reported a relationship between alterations in different amino acids and derivatives involved in neurotransmission systems and cognitive impairment. Therefore, in this study the neurotransmission impairment associated to early AD has been evaluated. For this purpose, different amino acids and derivatives were determined in saliva samples from AD patients and healthy subjects, by means of an analytical method based on chromatography coupled to tandem mass spectrometry. Results showed statistically significant differences in salivary levels for the compounds myo-inositol, creatine and acetylcholine; and other compounds (myo-inositol, glutamine, creatine, acetylcholine) showed significant correlations with some cognitive tests scores. Therefore, these compounds were included in a multivariate analysis and the corresponding diagnosis model showed promising indices (AUC 0.806, sensitivity 61%, specificity 92%). In conclusion, some amino acids and derivatives involved in neurotransmission impairment could be potential biomarkers in early and non-invasive AD detection.

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Section: Discussionsupporting

confidence: 72%

Early neurotransmission impairment in non-invasive Alzheimer Disease detection

Peña-Bautista

Torres-Cuevas

Baquero

et al. 2020

Sci Rep

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“…OPCs establish physical contacts with functionally relevant neuronal domains and form in parallel with neuronal synaptogenesis, including dendrites, somata, nodes of Ranvier and synaptic cleft [110][111][112]. It has been shown that elevated glutamate levels and gene expression of glutamate receptors are found in the plasma, cerebrospinal fluid (CSF) and locus coeruleus of postmortem brains from patients with depression [113]. Although the pathological mechanism is unclear, researchers found that MDD patients treated with the antidepressant venlafaxine demonstrated decreased glutamate levels in CSF, indicating a correlation between the attenuation or dysfunction of the glutamatergic system and antidepressant treatment of MDD [114].…”

Section: Neurotransmitters and Their Receptors In Depressionmentioning

confidence: 99%

Oligodendrocyte lineage cells and depression

et al. 2020

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Depression is a common mental illness, affecting more than 300 million people worldwide. Decades of investigation have yielded symptomatic therapies for this disabling condition but have not led to a consensus about its pathogenesis. There are data to support several different theories of causation, including the monoamine hypothesis, hypothalamic–pituitary–adrenal axis changes, inflammation and immune system alterations, abnormalities of neurogenesis and a conducive environmental milieu. Research in these areas and others has greatly advanced the current understanding of depression; however, there are other, less widely known theories of pathogenesis. Oligodendrocyte lineage cells, including oligodendrocyte progenitor cells and mature oligodendrocytes, have numerous important functions, which include forming myelin sheaths that enwrap central nervous system axons, supporting axons metabolically, and mediating certain forms of neuroplasticity. These specialized glial cells have been implicated in psychiatric disorders such as depression. In this review, we summarize recent findings that shed light on how oligodendrocyte lineage cells might participate in the pathogenesis of depression, and we discuss new approaches for targeting these cells as a novel strategy to treat depression.

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“…Their data suggest that CSF glutamate and glutamine levels might serve as a subclinical biomarker of subtle cognitive changes. 37 Further to this, in the brain, most endogenous glutamine is produced by glutamine synthetase (GS). Increased levelsbut compromised activityof GS may explain the increased levels of CSF glutamine in Alzheimer's disease patients.…”

Section: Biological Plausibilitymentioning

confidence: 99%

<p>Circulating Glutamine and Alzheimer’s Disease: A Mendelian Randomization Study</p>

Adams¹

2020

CIA

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Video abstractPoint your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use:https://youtu.be/nvEXdk_hzgcBackground: Alzheimer's disease is a devastating neurodegenerative disorder. Its worldwide prevalence is over 24 million and is expected to double by 2040. Finding ways to prevent its cognitive decline is urgent.Methods: A two-sample Mendelian randomization study was performed instrumenting glutamine, which is abundant in blood, capable of crossing the blood-brain barrier, and involved in a metabolic cycle with glutamate in the brain. Results:The results reveal a protective effect of circulating glutamine against Alzheimer's disease (inverse-variance weighted method, odds ratio per 1-standard deviation increase in circulating glutamine = 0.83; 95% CI 0.71, 0.97; P = 0.02).Conclusion: These findings lend credence to the emerging story supporting the modifiability of glutamine/glutamate metabolism for the prevention of cognitive decline. More circulating glutamine might mean that more substrate is available during times of stress, acting as a neuroprotectant. Modifications to exogenous glutamine may be worth exploring in future efforts to prevent and/or treat Alzheimer's disease.

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Elevated Glutamate and Glutamine Levels in the Cerebrospinal Fluid of Patients With Probable Alzheimer's Disease and Depression

Cited by 139 publications

References 71 publications

Early neurotransmission impairment in non-invasive Alzheimer Disease detection

Early neurotransmission impairment in non-invasive Alzheimer Disease detection

Oligodendrocyte lineage cells and depression

<p>Circulating Glutamine and Alzheimer’s Disease: A Mendelian Randomization Study</p>

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