Brain Glutathione Levels – A Novel Biomarker for Mild Cognitive Impairment and Alzheimer’s Disease

@article{Mandal2015BrainGL,
  title={Brain Glutathione Levels – A Novel Biomarker for Mild Cognitive Impairment and Alzheimer’s Disease},
  author={Pravat Kumar Mandal and Sumiti Saharan and Manjari Tripathi and Geetanjali Murari},
  journal={Biological Psychiatry},
  year={2015},
  volume={78},
  pages={702-710}
}
BACKGROUND Extant data from in vivo animal models and postmortem studies indicate that Alzheimer's disease (AD) pathology is associated with reduction of the brain antioxidant glutathione (GSH), yet direct clinical evidence has been lacking. In this study, we investigated GSH modulation in the brain with AD and assessed the diagnostic potential of GSH estimation in hippocampi (HP) and frontal cortices (FC) as a biomarker for AD and its prodromal stage, mild cognitive impairment (MCI). METHODS… Expand
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References

SHOWING 1-10 OF 61 REFERENCES
Peripheral levels of glutathione and protein oxidation as markers in the development of Alzheimer's disease from Mild Cognitive Impairment
TLDR
It is shown that some peripheral markers of oxidative stress appear in MCI with a similar pattern to that observed in AD, which suggests that oxidative stress might represent a signal of the AD pathology. Expand
The emerging role of glutathione in Alzheimer's disease.
TLDR
The present manuscript integrates findings from various studies to elucidate the possible molecular mechanisms through which disruptions in GSH homeostasis may contribute to AD pathology. Expand
Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study
TLDR
The association between pathological CSF and progression to Alzheimer's disease was much stronger than, and independent of, established risk factors including age, sex, education, APOE genotype, and plasma homocysteine. Expand
Brain oxidative stress: detection and mapping of anti-oxidant marker 'Glutathione' in different brain regions of healthy male/female, MCI and Alzheimer patients using non-invasive magnetic resonance spectroscopy.
TLDR
In vivo detection of GSH non-invasively from various brain regions in bilateral hemispheres of healthy male and female subjects and from bi-lateral frontal cortices in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) is reported. Expand
Lower levels of glutathione in the brains of secondary progressive multiple sclerosis patients measured by 1H magnetic resonance chemical shift imaging at 3 T
TLDR
The lower GSH levels in patients with secondary progressive multiple sclerosis indicate the presence of oxidative stress in SPMS, which could be at least partially responsible for ongoing functional decline in these patients. Expand
Oxidative imbalance in patients with mild cognitive impairment and Alzheimer's disease
TLDR
A pattern characterized by increased tHcy levels and decreased TAC is present in AD as well as MCI patients, and ROS levels appear to be correlated with age rather than with a specific dementing disorder, thus leading to the hypothesis that oxidative imbalance observed in AD could be due to a decreases TAC. Expand
Gender differences in glutathione metabolism in Alzheimer's disease
TLDR
It was shown for the first time that GSH metabolism was regulated differently in male and female AD patients, suggesting that a decreased de novo GSH synthetic capacity is responsible for the decline in GSH content in AD. Expand
Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer’s disease
TLDR
As MCI may represent a prodromal stage of AD, and oxidative damage appears to occur as one of the earliest pathophysiological events in AD, an increased intake of antioxidants in patients with MCI could be helpful in lowering the risk of conversion to dementia. Expand
Evidence of increased oxidative damage in subjects with mild cognitive impairment
TLDR
Oxidative damage occurs in the brain of subjects with mild cognitive impairment, suggesting that oxidative damage may be one of the earliest events in the onset and progression of Alzheimer disease. Expand
Elevated Oxidative Stress and Decreased Antioxidant Function in the Human Hippocampus and Frontal Cortex with Increasing Age: Implications for Neurodegeneration in Alzheimer’s Disease
TLDR
It is suggested that the regions HC and FC are subjected to widespread oxidative stress, loss of antioxidant function and enhanced GFAP expression during aging which might make them more susceptible to deranged physiology and selective neuronal degeneration. Expand
...
1
2
3
4
5
...