Evidence against increased glycoxidation in patients with Alzheimer's disease

Neuropathological findings of Alzheimer's disease (AD) are intracellular (neurofibrillary tangles) and extracellular (senile plaques) filamentous protein aggregates. Non-enzymatic glycation has been proposed as a primary factor in this pathogenesis, leading to increased insolubility of tau protein and beta-amyloid. The aim of our study was to test the hypothesis that increased glycoxidation, i.e. increased levels of oxidized products from non-enzymatic glycation could be found in brains of patients with AD and of aged Down syndrome (DS) subjects with abundant AD-like neuropathological lesions. Frontal cortex specimens were assayed for pentosidine (Pent) and N-epsilon-carboxymethyl-lysine (CML) by reversed phase high performance liquid chromatographical methods. Pent and CML levels in AD (n = 10; Pent, 35.5 +/- 4.84 mumol/g wet-weight tissue; CML, 135.2 +/- 5.0 mumol/g wet-weight tissue) were comparable to DS (n = 9; Pent, 36.4 +/- 3.21; CML, 133.5 +/- 4.7) and controls (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 glycoxidation in AD compared to normal aging.