Journal
NEUROBIOLOGY OF AGING
Volume 29, Issue 2, Pages 185-193Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2006.10.017
Keywords
fetal hemoglobin; gamma globin; methemoglobin; heme; neurological; vascular disease; polymorphism; amyloid
Categories
Funding
- NIA NIH HHS [U24 AG021886] Funding Source: Medline
- NINDS NIH HHS [R29NS32835-01, R01 NS045934-05, R01-NS045934-05, R01 NS045934] Funding Source: Medline
Ask authors/readers for more resources
From a normal human brain phage display library screen we identified the gamma (A)-globin chain of fetal hemoglobin (HbF) as a protein that bound strongly to A beta 1-42. We showed the oxidized form of adult Hb (metHb A) binds with greater affinity to A beta 1-42 than metHb F. MetHb is more toxic than oxyhemoglobin because it loses its heme group more readily. Free Hb and heme readily damage vascular endothelial cells similar to Alzheimer's disease (AD) vascular pathology. The XmnI polymorphism (C -> T) at -158 of the gamma (G)-globin promoter region can contribute to increased Hb F expression. Using family-based association testing, we found a significant protective association of this polymorphism in the NIMH sibling dataset (n = 489) in families, with at least two affected and one unaffected sibling (P = 0.006), with an age of onset >50 years (p = 0.010) and >65 years (p = 0.013), and families not homozygous for the APOE4 allele (P = 0.041). We hypothesize that Hb F may be less toxic than adult Hb in its interaction with A beta and may protect against the development of AD. (C) 2006 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available