Isotopic Evidence for Disrupted Copper Metabolism in Amyotrophic Lateral Sclerosis

Summary: Redox-active metals are thought to be implicated in neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). To address this point, we measured the concentrations of 12 elements and, for the first time, the stable isotope compositions of copper (redox-active) and zinc (redox-inactive) in human cerebrospinal fluids of 31 patients with ALS, 11 age-matched controls (CTRL), and 14 patients with Alzheimer disease. We first show that metal concentrations weakly discriminate patients with ALS from the two other groups. We then report that zinc isotopic compositions are similar in the three groups, but that patients with ALS have significantly 65copper-enriched isotopic compositions relative to CTRL and patients with AD. This result unambiguously demonstrates that copper is implicated in ALS. We suggest that this copper isotopic signature may result from abnormal protein aggregation in the brain parenchyma, and propose that isotopic analysis is a potential tool that may help unraveling the molecular mechanisms at work in ALS. : Nuclear Medicine; Isotope Chemistry; Neuroscience; Clinical Neuroscience Subject Areas: Nuclear Medicine, Isotope Chemistry, Neuroscience, Clinical Neuroscienc

Interdisciplinary Case Study: Geochemistry Meets the Clinic in Search for a Metal ALS Biomarker

International audienc

Nonlinearity of bituminous materials for small amplitude cyclic loadings

Photograph of competitors in the 1997 National Cutting Horse Association Summer Cutting Spectacular held at Will Rogers Coliseum in Fort Worth, Texas