title: Carbon monoxide and iron modulate plasmatic coagulation in Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a significant source of morbidity and mortality for millions of people worldwide, and multiple potential etiologies have been postulated to contribute to AD. Among these, spontaneous cerebral emboli and increased cerebral and circulating heme oxygenase (Hmox) activity in AD patients are of particular interest, as two of the products of Hmox activity, carbon monoxide (CO) and iron enhance plasmatic coagulation and modify the ultrastructure of thrombi. We hypothesized that patients afflicted with AD would have coagulation kinetics modulated by CO and iron. Using viscoelastic assessments of coagulation, it was determined with a small cohort (n=11) of AD patients that all had enhancement of coagulation by CO, iron, or both. In a complementary fashion, it was determined that a separate cohort (n=12) of AD patients had thrombi with ultrastructural features consistent with iron and CO exposure as assessed with scanning electron microscopy. Further, when stratified by normal or abnormally increased serum ferritin concentrations (which can be increased by Hmox), the AD patients with abnormal ferritin concentrations had significantly thinner fibrin fiber diameters, not unlike that noted when normal plasma is mixed with iron or CO. In sum, AD patients were noted to have plasmatic coagulation kinetic and thrombus ultrastructural changes consistent with exposure to CO and iron. Future investigation of CO and iron in the pathogenesis of Alzheimer's disease is warranted.
authors.forename: Vance G
authors.initials: VG
authors.lastname: Nielsen
authors.forename: Etheresia
authors.initials: E
authors.lastname: Pretorius
authors.forename: Janette
authors.initials: J
authors.lastname: Bester
authors.forename: Wayne K
authors.initials: WK
authors.lastname: Jacobsen
authors.forename: Patrick K
authors.initials: PK
authors.lastname: Boyle
authors.affiliation: Department of Anesthesiology, the University of Arizona College of Medicine, P.O. Box 245114; 1501 North Campbell Avenue, Tucson, AZ 85724-5114, USA. vgnielsen@email.arizona.edu.
authors.forename: Joao P
authors.initials: JP
authors.lastname: Reinhard
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood*; D001777:Blood Coagulation / Q000187:drug effects*; D002248:Carbon Monoxide / Q000494:pharmacology*; D015331:Cohort Studies; D005260:Female; D005293:Ferritins / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000494:pharmacology*; D008297:Male; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D010949:Plasma / Q000000981:diagnostic imaging / Q000378:metabolism; D011877:Radionuclide Imaging; D013917:Thrombin / Q000378:metabolism
chemical_list: D002248:Carbon Monoxide; D005340:Fibrinogen; D005293:Ferritins; D007501:Iron; D013917:Thrombin