Glutathione level variations in brain and blood in healthy aging and Alzheimer’s disease continuum: A systematic review

Abstract

AbstractBackgroundOxidative stress (OS) plays an important role in healthy and pathological aging, particularly Alzheimer’s disease (AD). To protect against the harmful effects of OS, the body uses antioxidants, the most prevalent being glutathione (reduced form, GSH) (Dwivedi et al., 2020). The consistency of GSH perturbations with age and in the AD continuum has not been systematically assessed. We address this knowledge gap by conducting a systematic review of GSH variations in brain and blood in healthy aging and the AD continuum.MethodPubMed searches were conducted up to January 2023. 15 keyword combinations were used to identify studies investigating GSH levels in (i) brain (in‐vivo using magnetic resonance spectroscopy (MRS) and in autopsy tissue using biochemical assays) and/or (ii) blood (plasma, serum) using biochemical assays (Fig1A,B). We considered individuals between 18‐39 years (yrs) as young‐adults, 40‐59 yrs as middle‐aged, and ≥60 yrs as old‐adults.Result42 studies met inclusion criteria (Fig1A,B; Fig2). BRAIN : Good to excellent reproducibility was reported by 12 MRS studies (3T, N = 6; 4T, N = 1; 7T, N = 5). For studies investigating age‐specific changes in cognitively unimpaired adults (CU, N = 6), GSH levels were significantly reduced in the majority (50%; temporal, occipital, limbic) of ROIs investigated in old‐ relative to young‐ or middle‐aged adults. Relative to CU, while brain GSH levels were reported to be lower by the majority (5/7) of AD dementia studies, MCI studies lacked consensus, with decreases (N = 3), increases (N = 2) and no significant change (N = 2) reported. BLOOD : Blood GSH levels were lower with increasing age in CU (5/7), and further decreased in patients (5/7).In both brain and blood, the majority (4/7) of AD continuum studies assessing cognition reported poorer cognitive functions with lower GSH levels.ConclusionOur systematic review demonstrates that (a) in‐vivo MRS measurements of GSH are reliable; (b) GSH levels in CU generally decrease with increasing age; and (c) GSH levels are reduced in AD relative to age‐matched CU, and reduced GSH is associated with cognitive impairment. Interventions to increase GSH levels may therefore have beneficial effects in AD.