Abstract
Oxidative stress (OS) plays an important role in Alzheimer's disease (AD) and glutathione (GSH) mitigates this effect by maintaining redox‐imbalance and free‐radical neutralization. Quantified brain GSH concentration provides distinct information about OS among age‐matched normal control (NC), mild cognitive impairment (MCI) and AD patients. We report alterations of in vivo GSH conformers, along with the choline, creatine, and N‐acetylaspartate levels in the cingulate cortex (CC) containing anterior (ACC) and posterior (PCC) regions of 64 (27 NC, 19 MCI, and 18 AD) participants using MEscher–GArwood‐Point‐RESolved spectroscopy sequence. Result indicated, tissue corrected GSH depletion in PCC among MCI (p = .001) and AD (p = .028) and in ACC among MCI (p = .194) and AD (p = .025) as compared to NC. Effects of the group, region, and group × region on GSH with age and gender as covariates were analyzed using a generalized linear model with Bonferroni correction for multiple comparisons. A significant effect of group with GSH depletion in AD and MCI was observed as compared to NC. Receiver operator characteristic (ROC) analysis of GSH level in CC differentiated between MCI and NC groups with an accuracy of 82.8% and 73.5% between AD and NC groups. Multivariate ROC analysis for the combined effect of the GSH alteration in both ACC and PCC regions provided improved diagnostic accuracy of 86.6% for NC to MCI conversion and 76.4% for NC to AD conversion. We conclude that only closed GSH conformer depletion in the ACC and PCC regions is critical and constitute a potential biomarker for AD.
Highlights
Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative brain disorder that affects millions of people worldwide
We presented the antioxidant hypometabolism with the quantified GSH levels in both anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC) regions using MEGA-PRESS sequence, where PCC shows higher depletion of GSH than the ACC region in both mild cognitive impairment (MCI) and AD patients, as compared to normal control (NC)
In another magnetic resonance spectroscopy (MRS) study involving MCI subjects, it was found that GSH level in both the ACC and PCC regions increases in MCI patients compared to healthy control (HC) and this increase in GSH level was explained as an early compensatory or neuroprotective response (Duffy et al, 2014)
Summary
Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative brain disorder that affects millions of people worldwide. Detailed autopsy study involving AD, Parkinson's disease (PD), and dementia with Lewy bodies (DLB) have presented that the GSH level in the cingulate cortex (CC) region is depleted in AD patients by 49% as compared to age-matched controls (Gu et al, 1998). The postmortem (five SuperAgers, five elderly, and five MCI) investigation on the cingulate region suggested strong correlation (p < .05) of neuronal density with the memory capacity in advanced old age participants with better episodic memory function (SuperAgers) than the average elderly and MCI (Gefen et al, 2015) Another autopsy study of definite AD patients (N = 31) has reported a significant positive correlation in apathy and neurofibrillary tangles in ACC brain region (Tekin et al, 2001). This novel scheme of multiple metabolite detection and quantitation from single noninvasive MRS data acquisition broadens the use of MEGAPRESS pulse sequence in clinical setting
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