Methylglyoxal, glyoxal, and their detoxification in Alzheimer's disease.
The accumulation of advanced glycation end products (AGEs) in brains with Alzheimer's disease (AD) has been implicated in the formation of insoluble deposits such as amyloid plaques and neurofibrillary tangles. AGEs are also known to activate glia, resulting in inflammation and neuronal dysfunction. As reactive intermediates of AGE formation, neurotoxic reactive dicarbonyl compounds such as glyoxal and methylglyoxal have been identified. One of the most effective detoxification systems for methylglyoxal and glyoxal is the glutathione-dependent glyoxalase system, consisting of glyoxalase I and glyoxalase II. In this study, we have determined the methylglyoxal and glyoxal levels in the cerebrospinal fluid of AD patients compared to healthy controls. Methylglyoxal levels in AD patients were twofold higher than in controls, but this difference was not significant due to the large intergroup variations and the small sample size. However, the concentrations of both compounds were five to seven times higher in CSF than in plasma. We also investigated the glyoxalase I level in AD and healthy control brains. The number of glyoxalase I- positive neurons were increased in AD brains compared to controls. Our findings suggest that glyoxalase I is upregulated in AD in a compensatory manner to maintain physiological methylglyoxal and glyoxal levels.
Kuhla
Björn
B
Interdisciplinary Centre of Clinical Research (IZKF), Neuroimmunological Cell Biology Unit, University of Leipzig, Inselstrasse 22, D- 04103 Leipzig, Germany. kuhb@medizin.uni-leipzig.de
Lüth
Hans-Joachim
HJ
Haferburg
Dietrich
D
Boeck
Katharina
K
Arendt
Thomas
T
Münch
Gerald
G
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D002540:Cerebral Cortex / Q000201:enzymology; D005260:Female; D006037:Glyoxal / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D006801:Humans; D008658:Inactivation, Metabolic; D007791:Lactoylglutathione Lyase / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011765:Pyruvaldehyde / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D012016:Reference Values
D006037:Glyoxal; D011765:Pyruvaldehyde; D007791:Lactoylglutathione Lyase