EVIDENCE AGAINST INCREASED GLYCOXIDATION IN PATIENTS WITH ALZHEIMERS-DISEASE

Neuropathological findings of Alzheimer's disease (AD) are intracellul ar (neurofibrillary tangles) and extracellular (senile plaques) filame ntous protein aggregates. Non-enzymatic glycation has been proposed as a primary factor in this pathogenesis, leading to increased insolubil ity of tau protein and P-amyloid. The aim of our study was to test the hypothesis that increased glycoxidation, i.e. increased levels of oxi dized products from non-enzymatic glycation could be found in brains o f patients with AD and of aged Down syndrome (DS) subjects with abunda nt AD-like neuropathological lesions. Frontal cortex specimens were as sayed for pentosidine (Pent) and N-epsilon-carboxymethyl-lysine (CML) by reversed phase high performance Liquid chromatographical methods. P ent and CML levels in AD (n = 10; Pent, 35.5 +/- 4.84 mu mol/g wet-wei ght tissue; CML, 135.2 +/- 5.0 mu mol/g wet-weight tissue) were compar able to DS (n = 9; Pent, 36.4 +/- 3.21; CML, 133.5 +/- 4.7) and contro ls (n = 10; Pent, 35.2 +/- 3.55; CML, 136.9 +/- 3.3). We conclude that the results are not compatible with the concept of increased glycoxid ation in AD compared to normal aging. (C) 1997 Elsevier Science Irelan d Ltd.