182 - Noninvasively Measured Human Brain Glutathione and Ascorbate Concentrations in Healthy Aging and in Alzheimer's Disease

Abstract

Numerous studies have found lower levels of antioxidants in the blood and cerebrospinal fluid of elderly adults. Oxidative stress is involved in Alzheimer’s disease (AD) pathogenesis and progression. Increased sensitivity of magnetic resonance technology has made it possible to noninvasively quantify concentrations of the antioxidants glutathione (GSH) and ascorbate (Asc) in intact human brain. Ultra-high field magnetic resonance spectroscopy (MRS) was used to measure concentrations of GSH and ascorbate in the occipital cortex (OCC) and posterior cingulate cortex (PCC) of seventeen young adults, sixteen cognitively normal older adults, and eight patients with AD. The short-echo-time MRS approach inherently retained numerous resonances, from which a profile of 15 neurochemicals was measured. For the first time, the concentration of GSH was found to be lower (p = 0.02) in the OCC of the elderly in a way that is not contingent upon the transverse relaxation rate. Healthy aging tended to impact neurochemicals associated with excitotoxicity (i.e. N-acetylaspartate) in the OCC, whereas those more closely linked to reactive astrogliosis (i.e.,myo-inositol, creatine and choline) were impacted in the PCC. The concentration of Asc was lower (p = 0.005) in the PCC of the patients with AD than in the healthy older adults. This is the first time human brain Asc has been studied noninvasively in patients with AD. In patients, one of the neurochemicals associated with reactive astrogliosis (myo-inositol) was higher in the OCC and two were higher in the PCC (i.e., myo-inositol and choline). Taken together, these outcomes show that both aging and AD impact brain regions differentially. These findings fill part of the gap in understanding how the brain deteriorates throughout aging and AD. Ultra-high field ultra-short-echo-time MRS supplies hitherto missing steps along the pathway to preventing and treating cognitive decline, i.e. means to identify which antioxidant is compromised, in which brain region, in whom, and whether intervention can achieve normalization.