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Cerebral Cortex Advance Access published online on July 6, 2004

Cerebral Cortex, doi:10.1093/cercor/bhh123
© 2004 by Oxford University Press
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Article

Age- and Stage-dependent Accumulation of Advanced Glycation End Products in Intracellular Deposits in Normal and Alzheimer's Disease Brains

Hans-Joachim Lüth 1*, Vera Ogunlade 2, Björn Kuhla 3, Rosemarie Kientsch-Engel 4, Peter Stahl 4, Julie Webster 5, Thomas Arendt 1, Gerald Münch 3

1 Department of Neuroanatomy, Paul Flechsig Institute of Brain Research, University of Leipzig, Jahnallee 59, 04109 Leipzig, Germany
2 Department of Neuropathology, Institute of Pathology, University of Leipzig, Liebigstrasse 26, 04103 Leipzig, Germany
3 Neuroimmunological Cell Biology Unit, IZKF Leipzig, Inselstrasse 22, 04103 Leipzig, Germany
4 Roche Diagnostics GmbH, 82372 Penzberg, Germany
5 Comparative Genomics Centre, James Cook University, Townsville 4811, Australia

* To whom correspondence should be addressed. E-mail: lueth{at}medizin.uni-leipzig.de.


   Abstract

In this immunohistochemical study, the age- and stage-dependent accumulation of advanced glycation end-products (AGEs) in Alzheimer's disease (AD) and their relation to the formation of neurofibrillary tangles and neuronal cell death was investigated. For this purpose, the distribution of AGEs in neurons and glia was analyzed in the auditory association area of superior temporal gyrus (Brodmann area 22) of young and old non-demented controls and compared with early- and late-stage AD. A possible co-localization of AGEs with typical hallmarks of AD, such as hyperphosphorylated tau (as a marker for disturbed kinase/phosphatase activity), nNOS (as a marker for nitroxidative stress) and caspase-3 (as a marker of apoptotic cell death), was also investigated. Our results show that the percentage of AGE-positive neurons (and astroglia) increase both with age and, in AD patients, with the progression of the disease (Braak stages). Interestingly, nearly all if those neurons which show diffuse cytosolic AGE immunoreactivity also contain hyperphosphoryated tau, suggesting a link between AGE accumulation and the formation of early neurofibrillary tangles. Many, but not all, neurons show a co-localization of AGEs with other markers of neurodegeneration, such as nNOS and caspase-3.

Keywords: advanced glycation endproducts; Alzheimer's disease; Braak stages; neurofibrillary tangles; nitric oxide.
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