Increased protein glycation in cerebrospinal fluid of Alzheimer's disease

Accumulation of advanced glycation end products occurs in the brain with ag eing and was proposed to be involved in pathogenesis of Alzheimer's disease . We studied changes in the level of an early glycation product, an Amadori product, in cerebrospinal fluid (CSF) in ageing and in late-onset Alzheime r's disease. The work was carried out on 99 consecutive patients. The conce ntration of Amadori product in CSF correlated with CSF glucose concentratio n but was not changed with age (n = 70). In contrast, level of CSF Amadori product was 1.7-fold higher in Alzheimer's disease patients (n = 29) as com pared with non-demented age-matched control group (n = 20; P < 0.0005), alt hough CSF glucose concentration was similar in both groups (4.1 +/- 1.3 vs. 3.8 +/- 0.6 mmol/liter, reap.). An increased accumulation of Amadori produ cts was found in all major proteins of CSF of Alzheimer's disease including albumin, apolipoprotein E and transthyretin. We propose that the increased early glycation of CSF proteins in the Alzheimer's patients may stimulate the formation and the consequent deposition of advanced glycation end produ cts as well as oxidative stress in the brain. (C) 2001 Elsevier Science Inc . All rights reserved.