Transferrin and Iron in Normal, Alzheimer's Disease, and Parkinson's Disease Brain Regions

Abstract: Oxidant-mediated damage is suspected to be involved in the pathogenesis of several neurodegenerative disorders. Iron promotes conversion of hydrogen peroxide to hydroxyl radical and, thus, may contribute to oxidant stress. We measured iron and its transport protein transferrin in caudate, putamen, globus pallidus, substantia nigra, and frontal cortex of subjects with Alzheimer's disease (n = 14) and Parkinson's disease (n = 14), and in younger adult (n = 8) and elderly (n = 8) normal controls. Although there were no differences between control groups with regard to concentrations of iron and transferrin, iron was significantly increased ( p < 0.05) in Alzheimer's disease globus pallidus and frontal cortex and Parkinson's disease globus pallidus, and transferrin was significantly increased in Alzheimer's disease frontal cortex, compared with elderly controls. The transferrin/iron ratio, a measure of iron mobilization capacity, was decreased in globus pallidus and caudate in both disorders. Regional transferrin and iron concentrations were generally more highly correlated (Pearson's correlation coefficient) in elderly controls than in Alzheimer's and Parkinson's disease. The altered relationship between iron and transferrin provides further evidence that a disturbance in iron metabolism may be involved in both disorders.     

Effects of Age,Sex, and Polycystic Disease on Progressive Bone Disease of Renal Failure

A study of 150 patients undergoing haemodialysis has shown that age had a striking effect on the radiological presentation of renal bone disease, erosions being common in the young and uncommon in older patients and vascular calcification showing opposite trends to this. Men aged 20 to 59 years had a greater tendency to develop erosions than did women in this age range. Examination of a group of 53 patients over a period of five years showed that the half time for the development of vascular calcification was 4·6 years, erosions 26·7 years, and fractures 6·9 years. Nine out of 16 polycystic patients matched for age and sex with 50 controls did not develop erosions and had consistently less vascular calcification than the controls when examined over a six-year period.     

Obesity,End‐stage Renal Disease,and Survival in an Elderly Cohort With Cardiovascular Disease

Obesity is highly prevalent in African Americans and is associated with increased risk of End‐Stage Renal Disease (ESRD) and death. It is not known if the effect of obesity is similar among blacks and whites. The aim of this study is to examine racial differences in the association of obesity with ESRD and survival in elderly patients (age >65). Data were obtained for 74,167 Medicare patients with acute myocardial infarction (AMI) between February 1994 and July 1995. BMI was calculated as weight (kg) divided by height (m²). We evaluated the association of BMI class with ESRD incidence and death using multivariable Cox proportional hazards models, testing for race‐BMI interactions. Compared to whites, African Americans had higher BMI (26.9 vs. 26.0, P < 0.0001) and estimated glomerular filtration rate (72.4 ml/min/1.73 m² vs. 66.6 ml/min/1.73 m², P < 0.0001). Crude ESRD rates increased with increasing obesity among whites but not among blacks. However, after adjusting for age, sex, and other comorbidities, obesity was not associated with increased ESRD rate among blacks or whites and the interaction between race and BMI was not significant. Furthermore, for both races, patients classified as overweight, class 1 obese, or class 2 obese had similar, significantly better survival abilities compared to normal weight patients and the race BMI interaction was not significant. In conclusion, obesity does not increase risk of ESRD among black or white elderly subjects with cardiovascular disease (CVD). However, both obese blacks and whites, in this population, experience a survival benefit. Further studies need to explore this obesity paradox.     

Mutations in Smooth Muscle Alpha-Actin (ACTA2) Cause Coronary Artery Disease, Stroke, and Moyamoya Disease, Along with Thoracic Aortic Disease

The vascular smooth muscle cell (SMC)-specific isoform of α-actin (ACTA2) is a major component of the contractile apparatus in SMCs located throughout the arterial system. Heterozygous ACTA2 mutations cause familial thoracic aortic aneurysms and dissections (TAAD), but only half of mutation carriers have aortic disease. Linkage analysis and association studies of individuals in 20 families with ACTA2 mutations indicate that mutation carriers can have a diversity of vascular diseases, including premature onset of coronary artery disease (CAD) and premature ischemic strokes (including Moyamoya disease [MMD]), as well as previously defined TAAD. Sequencing of DNA from patients with nonfamilial TAAD and from premature-onset CAD patients independently identified ACTA2 mutations in these patients and premature onset strokes in family members with ACTA2 mutations. Vascular pathology and analysis of explanted SMCs and myofibroblasts from patients harboring ACTA2 suggested that increased proliferation of SMCs contributed to occlusive diseases. These results indicate that heterozygous ACTA2 mutations predispose patients to a variety of diffuse and diverse vascular diseases, including TAAD, premature CAD, ischemic strokes, and MMD. These data demonstrate that diffuse vascular diseases resulting from either occluded or enlarged arteries can be caused by mutations in a single gene and have direct implications for clinical management and research on familial vascular diseases.