Role for glyoxalase I in Alzheimer's disease

Chen, Feng, Wollmer, M. Axel, Hoerndli, Frederic, Munch, Gerald, Kuhla, Bjorn, Rogaev, Evgeny I., Tsolaki, Magdalini, Papassotiropoulos, Andreas and Gotz, Juergen (2004) Role for glyoxalase I in Alzheimer's disease. National Academy of Sciences. Proceedings, 101 20: 7687-7692. doi:10.1073/pnas.0402338101

Author Chen, Feng
Wollmer, M. Axel
Hoerndli, Frederic
Munch, Gerald
Kuhla, Bjorn
Rogaev, Evgeny I.
Tsolaki, Magdalini
Papassotiropoulos, Andreas
Gotz, Juergen
Title Role for glyoxalase I in Alzheimer's disease
Journal name National Academy of Sciences. Proceedings   Check publisher's open access policy
ISSN 0027-8424
Publication date 2004-05-18
Sub-type Article (original research)
DOI 10.1073/pnas.0402338101
Open Access Status Not yet assessed
Volume 101
Issue 20
Start page 7687
End page 7692
Total pages 6
Place of publication Washington, DC, United States
Publisher National Academy of Sciences
Language eng
Formatted abstract
P301L mutant tau transgenic mice develop neurofibrillary tangles, a histopathologic hallmark of Alzheimer's disease and frontotemporal dementia (FTDP-17). To identify differentially expressed genes and to gain insight into pathogenic mechanisms, we performed a stringent analysis of the microarray dataset obtained with RNA from whole brains of P301L mutant mice and identified a single up-regulated gene, glyoxalase I. This enzyme plays a critical role in the detoxification of dicarbonyl compounds and thereby reduces the formation of advanced glycation end products. In situ hybridization analysis revealed expression of glyoxalase I in all brain areas analyzed, both in transgenic and control mice. However, levels of glyoxalase I protein were significantly elevated in P301L brains, as shown by Western blot analysis and immunohistochemistry. Moreover, a glyoxalase I-specific anti-serum revealed many intensely stained flame-shaped neurons in Alzheimer's disease brain compared with brains from nondemented controls. In addition, we examined a single nucleotide polymorphism predicting a nonconservative amino acid substitution at position 111 (E111A) in ethnically independent populations. We identified significant and consistent deviations from Hardy-Weinberg equilibrium, which points to the presence of selection forces. The E111A single nucleotide polymorphism was not associated with the risk for Alzheimer's disease in the overall population. Together, our data demonstrate the potential of transcriptomics applied to animal models of human diseases. They suggest a previously unidentified role for glyoxalase I in neurodegenerative disease.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Centre for Ageing Dementia Research Publications
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