{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:18:43Z","timestamp":1791980323552,"version":"4.4.0"},"reference-count":29,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2004,10,8]],"date-time":"2004-10-08T00:00:00Z","timestamp":1097193600000},"content-version":"vor","delay-in-days":3082,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[1996,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To determine whether the reduction in brain \u03b1\u2010ketoglutarate dehydrogenase complex activity in Alzheimer's disease (AD) is associated with an abnormality in one of its three constituent enzyme subunits, we measured protein levels of \u03b1\u2010ketoglutarate dehydrogenase (El), dihydrolipoamide succinyltransferase (E2), and dihydrolipoamide dehydrogenase (E3), in postmortem brain of 29 patients with AD (mean age, 73 years; age range of onset, 50\u201078 years) and 29 control subjects. In the AD group protein levels of all three subunits were significantly reduced by 23 to 41% in the temporal cortex, whereas in the parietal cortex (El: \u221228% E3: \u221232%) and hippocampus (E3: \u221233%) significant changes were limited to El and E3. \u03b1\u2010Ketoglutarate dehydrogenase complex activities were more markedly reduced (by 46\u201068%) and did not correlate with protein levels, suggesting that decreased enzyme activity cannot be primarily explained by loss of \u03b1\u2010ketoglutarate dehydrogenase complex protein. We did not find two E2 immunoreactive forms in the brain of any patient, as has been reported in fibroblasts of patients with very\u2010early\u2010onset chromosome 14\u2010linked AD. We conclude that brain protein and activity levels of \u03b1\u2010ketoglutarate dehydrogenase complex are reduced in patients with AD who have onset after 50 years and suggest that these changes, which are also observed in other human brain disorders, may represent a nonspecific consequence of different neurodegenerative processes. Nevertheless, reduced levels of this ratelimiting enzyme of the Krebs cycle could contribute to the brain neurodegenerative mechanisms of AD.<\/jats:p>","DOI":"10.1002\/ana.410390508","type":"journal-article","created":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T16:36:26Z","timestamp":1104597386000},"page":"592-598","source":"Crossref","is-referenced-by-count":113,"title":["Brain protein and \u03b1\u2010ketoglutarate dehydrogenase complex activity in alzheimer\u2010s disease"],"prefix":"10.1002","volume":"39","author":[{"given":"Frank","family":"Mastrogiacomo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Gordon","family":"Lindsay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucien","family":"Bettendorff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Rice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Kish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,10,8]]},"reference":[{"key":"e_1_2_1_2_2","first-page":"187","article-title":"Structure, aascmbly and function of mammalian \u03b1\u2010keto acid dehydrogenase complexes","volume":"9","author":"Koike M","year":"1976","journal-title":"Adv Biophys"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0968-0004(86)90033-2"},{"key":"e_1_2_1_4_2","first-page":"322","article-title":"Sequences directing dihydrolipoamide dehydrogenase (E3) binding are located on the 2\u2010oxoglutarate dehydrogenase (El) component of the mammalian 2\u2010oxoglutarate dehydrogenase multienzyme complex","volume":"11","author":"Rice JE","year":"1992","journal-title":"EMBO J"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1988.00520320022009"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00997071"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1993.tb07436.x"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410350311"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410310202"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1992.tb09439.x"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.41.4.479"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/118.1.185"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.51.4.552"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1986.tb09464.x"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1989.tb15002.x"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1975.tb11895.x"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410170505"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903460309"},{"key":"e_1_2_1_19_2","doi-asserted-by":"crossref","first-page":"19013","DOI":"10.1016\/S0021-9258(18)55164-4","article-title":"Purification and molecular cloning of succinyltransferase of the rat \u03b1a\u2010ketogluta rate dehydrogenase complex","volume":"266","author":"Nakano K","year":"1991","journal-title":"J Biol Chem"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(80)90220-7"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1988.00520320027010"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410130116"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1990.tb04948.x"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410390507"},{"key":"e_1_2_1_25_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2780423"},{"key":"e_1_2_1_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410350212"},{"key":"e_1_2_1_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1993.tb05668.x"},{"key":"e_1_2_1_28_2","doi-asserted-by":"crossref","unstructured":"MastrogiacomoF La MarcheJ DozicS et al.Immunoreactive levels of \u03b1\u2010ketoglutarate dehydrogenase subunits in Friedreich's ataxia and spinocerebellar ataxia type I. 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