Increased protein glycation in cerebrospinal fluid of Alzheimer's disease.
Accumulation of advanced glycation end products occurs in the brain with ageing 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 Alzheimer's disease. The work was carried out on 99 consecutive patients. The concentration of Amadori product in CSF correlated with CSF glucose concentration 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 compared with non-demented age-matched control group (n = 20; P < 0.0005), although CSF glucose concentration was similar in both groups (4.1 +/- 1.3 vs. 3.8 +/- 0.6 mmol/liter, resp.). An increased accumulation of Amadori products 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 products as well as oxidative stress in the brain.
Shuvaev
V V
VV
Centre du Médicament, INSERM U525, Université Henri Poincare Nancy I, 30, rue Lionnois, 54000, Nancy, France
Laffont
I
I
Serot
J M
JM
Fujii
J
J
Taniguchi
N
N
Siest
G
G
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000375:Aging / Q000134:cerebrospinal fluid / Q000378:metabolism; D000418:Albumins / Q000134:cerebrospinal fluid; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000378:metabolism*; D001057:Apolipoproteins E / Q000134:cerebrospinal fluid; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005947:Glucose / Q000134:cerebrospinal fluid; D017127:Glycation End Products, Advanced / Q000134:cerebrospinal fluid* / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D018384:Oxidative Stress; D011228:Prealbumin / Q000134:cerebrospinal fluid
D000418:Albumins; D001057:Apolipoproteins E; D017127:Glycation End Products, Advanced; D011228:Prealbumin; D005947:Glucose