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Oxidative stress affects all classes of macromolecules (sugar, lipids, proteins, and DNA), leading inevitably to neuronal dysfunction. We observed that N<jats:sup>\u03b5<\/jats:sup>\u2010(carboxymethyl)lysine (CML), the predominant advanced glycation end product that accumulates <jats:italic>in vivo<\/jats:italic>, along with its glycation\u2010specific precursor hexitol\u2010lysine, are increased in neurons from cases of Alzheimer's disease, especially those containing intracellular neurofibrillary pathology. The increase in hexitol\u2010lysine and CML can result from either lipid peroxidation or advanced glycation, whereas hexitol\u2010lysine is solely a product of glycation, suggesting that two distinct oxidative processes act in concert in the neuropathology of the disease. Furthermore, using olfactory neurons as an experimental model, we observed an increase in glycation products in neurons derived from Alzheimer's disease patients. Our findings support the idea that aldehyde\u2010mediated modifications, in concert with oxyradical\u2010mediated modifications, are critical early pathogenic factors in Alzheimer's disease.<\/jats:p>","DOI":"10.1196\/annals.1333.062","type":"journal-article","created":{"date-parts":[[2005,7,21]],"date-time":"2005-07-21T16:59:10Z","timestamp":1121965150000},"page":"545-552","source":"Crossref","is-referenced-by-count":153,"title":["Oxidative Stress and Neurodegeneration"],"prefix":"10.1111","volume":"1043","author":[{"given":"PAULA I.","family":"MOREIRA","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MARK A.","family":"SMITH","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XIONGWEI","family":"ZHU","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"AKIHIKO","family":"NUNOMURA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"RUDY J.","family":"CASTELLANI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GEORGE","family":"PERRY","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,1,9]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7742(08)60607-8"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.9.1565"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/59.11.1011"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/60.8.759"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/382120b0"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-08-02653.1997"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00309621"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1997.68052092.x"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2004.01.012"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.12.5710"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(95)93897-7"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(01)00570-6"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1532-0456(02)00119-9"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1995.64062660.x"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1989.tb09203.x"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.2475"},{"key":"e_1_2_6_18_2","first-page":"21639","article-title":"Modification of glucose\u20106\u2010phosphate dehydrogenase by 4\u2010hydroxy\u20102\u2010nonenal","volume":"269","author":"Friguet B.","year":"1994","journal-title":"Formation of cross-linked protein that inhibits the multicatalytic protease. 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