Metalloenzyme-like activity of Alzheimer's disease beta-amyloid. Cu-dependent catalytic conversion of dopamine, cholesterol, and biological reducing agents to neurotoxic H(2)O(2).

Beta-amyloid (Abeta) 1-42, implicated in the pathogenesis of Alzheimer's disease, forms an oligomeric complex that binds copper at a CuZn superoxide dismutase-like binding site. Abeta.Cu complexes generate neurotoxic H(2)O(2) from O(2) through Cu(2+) reduction, but the reaction mechanism has been unclear. We now report that Abeta1-42, when binding up to 2 eq of Cu(2+), generates the H(2)O(2) catalytically by recruiting biological reducing agents as substrates under conditions where the Cu(2+) or reducing agents will not form H(2)O(2) themselves. Cholesterol is an important substrate for this activity, as are vitamin C, L-DOPA, and dopamine (V(max) for dopamine = 34.5 nm/min, K(m) = 8.9 microm). The activity was inhibited by anti-Abeta antibodies, Cu(2+) chelators, and Zn(2+). Toxicity of Abeta in neuronal culture was consistent with catalytic H(2)O(2) production. Abeta was not toxic in cell cultures in the absence of Cu(2+), and dopamine (5 microm) markedly exaggerated the neurotoxicity of 200 nm Abeta1-42.Cu. Therefore, microregional catalytic H(2)O(2) production, combined with the exhaustion of reducing agents, may mediate the neurotoxicity of Abeta in Alzheimer's disease, and inhibitors of this novel activity may be of therapeutic value.

Particulate-phase mercury in the atmosphere: collectionl/analysis method development and applications

Particulate-phase mercury Hg(p) may constitute a small percentage of lhe total atmospheric mercury, but is thought to play na important role in deposition of mercury to terrestrial and aquatic ecosystems. This chapter presents techniques that have been utilized to collect and analyze Hg(p) in several recent projects including monitoring in Detroit and Ann Arbor, MI and during the Lake Michigan Urban Air Toxics Study. Fine (da <2.5 um) and total suspended particle (TSP) samples were collected and analyzed by two methods: (1) acid extraction followed by sparging and dual amalgamation cold vapor atomic fluorescence spectrometry, and (2) neutron activation analysis. The differences in Hg(p) detected ia the samples by these two analytical techniques, coupled with the size-segregated data collected, indicate that different foms of particulate mercury may be distinguished, and that differing physical/chemical properties may reflect potentially different sources.