期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：30
页码：11153-11158
DOI：10.1073/pnas.0404349101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Heme is a common factor linking several metabolic perturbations in Alzheimer's disease (AD), including iron metabolism, mitochondrial complex IV, heme oxygenase, and bilirubin. Therefore, we determined whether heme metabolism was altered in temporal lobes obtained at autopsy from AD patients and age-matched nondemented subjects. AD brain demonstrated 2.5-fold more heme-b (P < 0.01) and 26% less heme-a (P = 0.16) compared with controls, resulting in a highly significant 2.9-fold decrease in heme-a/heme-b ratio (P < 0.001). Moreover, the strong Pearson correlation between heme-a and heme-b measured in control individuals (r2 = 0.66, P < 0.002, n = 11) was abolished in AD subjects (r2 = 0.076, P = 0.39, n = 12). The level of ferrochelatase (which makes heme-b in the mitochondrial matrix) in AD subjects was 4.2 times (P < 0.04) that in nondemented controls, suggesting up-regulated heme synthesis. To look for a possible connection between these observations and established mechanisms in AD pathology, we examined possible interactions between amyloid {beta} (A{beta}) and heme. A{beta}(1-40) and A{beta}(1-42) induced a redshift of 15-20 nm in the spectrum of heme-b and heme-a, suggesting that heme binds A{beta
关键词：mitochondria ; heme-a ; iron ; clioquinol ; ferrochelatase
