Abstract
Glycation and advanced glycation endproducts (AGEs) are associated with Alzheimer’s Disease (AD) pathology. The protein glycation profile that characterises AD and the temporal nature of this modification are poorly defined and the impact of glycation on specific modified proteins is unclear. Here, the glycation profile was determined in brain tissue lysates from the temporal cortex of mild/moderate and severe AD and compared with age matched controls using Fluorescent boronic acid-PAGE (FluPAGE). Recombinant MIF was glycated and assayed for enzymatic activity. The cellular effects of MIF glycation were determined in primary mouse glial cell cultures. The glycated proteins in AD brain were identified as serum albumin, glial fibrillary acid protein, haemoglobin and MIF. MIF appeared as a doublet in AD, compared to a singlet in controls; due to glucose glycation and oxidation. This had a severe effect on MIF activity; attenuating tautomerase activity and inhibiting redox activity. Furthermore, glycation inhibited MIF-stimulated ERK phosphorylation in glial cells. MIF is an important immune regulatory molecule. Thus, glycation and oxidation of MIF could be part of an aberrant innate immune response in the early stages of AD. Furthermore, this selective modification of MIF in AD might have potential as a disease biomarker.
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