Abstract
Purpose: :
Metal dyshomeostasis plays a role in many diseases, including age-related macular degeneration (AMD), diabetes, and Alzheimer’s (AD). Recent reports have highlighted the role of unbound "free" copper in degenerative diseases using multiple, slow and inexpensive tests to arrive at only an estimate of the actual value. Further progress has been limited by lack of a technique to determine accurately and inexpensively non-ceruloplasmin bound free copper. We have developed such a device and report findings in AD, a disease known to be associated with severe vision loss.
Methods: :
Serum samples came from persons with AD diagnosed according to NINDS criteria (n= 37) and age-matched normals (n= 11). Samples were tested in a blind fashion. A 10 microL aliquot sample was loaded onto a test strip sensor, which isolates free copper for measurement. Total copper can also be determined. Data are shipped via USB to a computer for analysis. Ceruloplasmin was calculated by subtracting free copper from total copper and then multiplying the difference by 3 mg/microg. An independent statistician provided t-test, analysis of variance, and Means for Oneway Anova.
Results: :
Free copper in AD sera was nearly double that in normal sera as a percentage of total copper (AD 11.06% +/- 0.87; normal 6.60% +/- 1.59). Absolute free copper was similarly elevated (AD 14.48 +/-1.02 microg/dL ; normal 9.95 +/- 1.86 microg/dL). In contrast, neither mean total copper ( AD 150.07 microg/dL; normal 156.62 microg/dL), nor ceruloplasmin (AD 45.07 mg/dL; normal 48.89 mg/dL) differed.
Conclusions: :
Our findings using a novel direct measuring device confirm elevated free serum copper in AD, suggesting a role in pathogenesis since free copper produces severe tissue destruction, especially in the brain. The relatively higher free copper by percent suggests that AD patients may have abnormalities in their copper binding capacity. Our new technology should propel forward further studies of metal dyshomeostasis in AMD, diabetes, and other diseases. Supported by NIA -AG08017
Keywords: clinical (human) or epidemiologic studies: risk factor assessment • pathobiology • age-related macular degeneration