Plasma aminothiol compounds, but not serum tumor necrosis factor receptor II and soluble receptor for advanced glycation end products, are related to the cognitive impairment in Alzheimer's disease and mild cognitive impairment patients

Increasing evidence indicates that factors such as oxidative stress, plasma homocysteine increase and glutathione depletion, elevated pro-inflammatory cytokines and advanced glycation end products can play a role in Alzheimer's disease (AD) pathogenesis. The receptor for advanced glycation end products (RAGE) is a cell surface receptor that has been implicated in neurodegeneration, and a soluble isoform of RAGE (sRAGE) has the ability to prevent the adverse effects of RAGE signaling by acting as a decoy. Twenty-five patients with AD, 26 with mild cognitive impairment (MCI) and 44 age-matched control subjects were studied. All subjects were classified according to their clinical, cognitive and positron emission tomography study. Serum levels of sRAGE and TNF-alpha receptor II were not significantly different in AD or MCI patients compared to controls. Total plasma levels of glutathione and its metabolite cysteinglycine were decreased in AD and MCI patients compared to the control group. In addition, AD patients presented significantly in creased plasma homocysteine compared to those in MCI patients and controls. We found significant positive correlations between sRAGE and glutathione, cysteinglycine and cysteine levels. Moreover, a significant negative correlation between the total score of cognitive impairment and homocysteine levels, and significant positive correlations with glutathione, cysteinglycine and cysteine levels were observed. These findings indicate that plasma aminothiol compounds are associated with AD and MCI patients and with their cognitive status. Copyright (C) 2007 S. Karger AG, Basel.