title: Heme-a, the heme prosthetic group of cytochrome c oxidase, is increased in Alzheimer's disease.
abstract: Heme-a, is the heme prosthetic group of cytochrome c oxidase (COX), the terminal complex of the mitochondrial electron transport chain. We measured heme-a levels in postmortem brain tissue from nine patients diagnosed with dementia: Alzheimer's disease (AD) was the primary diagnosis in five, AD/diffuse Lewy body disease (DLBD) was diagnosed in two, DLBD was diagnosed in one, and DLBD (severe)/AD (mild) was diagnosed in one. Eight non-demented patients who died from non-neurological causes served as controls. When the primary diagnosis was AD (AD and AD/DLBD), levels of cerebral heme-a were increased almost two-fold on a protein basis compared to controls (p<0.001). Using perfused and non-perfused rats we showed that measured levels of cerebral heme-a were unaffected by the presence of blood in brain tissue. In mice we showed that levels of cerebral heme-a were unaffected by 24h of storage at 4 degrees C prior to freezing. These animal studies suggest that increased levels of cerebral heme-a in AD were not due to blood in postmortem brain or variation in postmortem interval.
authors.affiliation: Research Service, VA Medical Center, White River Junction, VT 05009-0001, USA. Barney.E.Dwyer@Dartmouth.EDU
authors.forename: Barney E
authors.initials: BE
authors.lastname: Dwyer
authors.forename: Meghan L
authors.initials: ML
authors.lastname: Stone
authors.forename: Nadia
authors.initials: N
authors.lastname: Gorman
authors.forename: Peter R
authors.initials: PR
authors.lastname: Sinclair
authors.forename: George
authors.initials: G
authors.lastname: Perry
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000201:enzymology*; D003576:Electron Transport Complex IV / Q000378:metabolism*; D005625:Frontal Lobe / Q000201:enzymology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D015415:Biomarkers; D021122:Protein Subunits; D003576:Electron Transport Complex IV