title: Active glycation in neurofibrillary pathology of Alzheimer disease: N(epsilon)-(carboxymethyl) lysine and hexitol-lysine.
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 N(epsilon)-(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.
authors: Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors: R J
authors: RJ
authors: Castellani
authors: P L
authors: PL
authors: Harris
authors: L M
authors: LM
authors: Sayre
authors: J
authors: J
authors: Fujii
authors: N
authors: N
authors: Taniguchi
authors: M P
authors: MP
authors: Vitek
authors: H
authors: H
authors: Founds
authors: C S
authors: CS
authors: Atwood
authors: G
authors: G
authors: Perry
authors: M A
authors: MA
authors: Smith
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D016022:Case-Control Studies; D005609:Free Radicals / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism*; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000378:metabolism* / Q000473:pathology*
chemical_list: D005609:Free Radicals; D017127:Glycation End Products, Advanced; C048496:N(6)-carboxymethyllysine; D008239:Lysine