Active glycation in neurofibrillary pathology of Alzheimer disease: Nε-(Carboxymethyl) lysine and hexitol-lysine

Rudy J. Castellani, Peggy L.R. Harris, Lawrence M. Sayre, Junichi Fujii, Naoyuki Taniguchi, Michael Peter Vitek, Hank Founds, Craig S. Atwood, George Perry*, Mark A. Smith

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

179 Scopus citations

Abstract

Advanced glycation end products are a diverse class of posttranslational modifications, stemming from reactive aldehyde reactions, that have been implicated in the pathogenesis of a number of degenerative diseases. Because advanced glycation end products are accelerated by, and result in formation of, oxygen-derived free radicals, they represent an important component of the oxidative stress hypothesis of Alzheimer disease (AD). In this study, we used in situ techniques to assess Nε-(Carboxymethyl)lysine (CML), the predominant advanced glycation end product that accumulates in vivo, along with its glycation-specific precursor hexitol-lysine, in patients with AD as well as in young and aged-matched control cases. Both CML and hexitol-lysine were increased in neurons, especially those containing intracellular neurofibrillary pathology in cases of AD. The increase in hexitol-lysine and CML in AD suggests that glycation is an early event in disease pathogenesis. In addition, because CML can result from either lipid peroxidation or advanced glycation, while hexitol-lysine is solely a product of glycation, this study, together with studies demonstrating the presence of 4-hydroxy-2-nonenal adducts and pentosidine, provides evidence of two distinct oxidative processes acting in concert in AD neuropathology. Our findings support the notion that aldehyde-mediated modifications, together with oxyradical-mediated modifications, are critical pathogenic factors in AD.

Original languageEnglish (US)
Pages (from-to)175-180
Number of pages6
JournalFree Radical Biology and Medicine
Volume31
Issue number2
DOIs
StatePublished - Jul 15 2001

Keywords

  • Advanced glycation end products
  • Alzheimer disease
  • Free radicals
  • Hexitol-lysine
  • N-(Carboxymethyl) lysine
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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