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PBT2 is a copper/zinc ionophore that rapidly restores cognition in mouse models of Alzheimer's disease (AD). A recent Phase IIa double-blind, randomized, placebo-controlled trial found that the 250 mg dose of PBT2 was well-tolerated, significantly lowered cerebrospinal fluid (CSF) levels of amyloid-beta42, and significantly improved executive function on a(More)
Transgenic expression of human amyloid beta (A beta) peptide in body wall muscle cells of Caenorhabditis elegans has been used to better understand aspects of Alzheimer disease (AD). In human aging and AD, A beta undergoes post-translational changes including covalent modifications, truncations, and oligomerization. Amino truncated A beta is increasingly(More)
The accumulation of amyloid-beta (Aβ) peptides is believed to be a central contributor to the neurodegeneration typically seen in Alzheimer's disease (AD) brain. Aβ extracted from AD brains invariably possesses extensive truncations, yielding peptides of differing N- and C-terminal composition. Whilst Aβ is often abundant in the brains of cognitively normal(More)
Decelerated degradation of beta-amyloid (Abeta) and its interaction with synaptic copper may be pathogenic in Alzheimer disease. Recently, Co(III)-cyclen tagged to an aromatic recognition motif was shown to degrade Abeta in vitro. Here, we report that apocyclen attached to selective Abeta recognition motifs (KLVFF or curcumin) can capture copper bound to(More)
Reducing amyloid-β peptide (Aβ) burden at the pre-symptomatic stages of Alzheimer’s disease (AD) is currently the advocated clinical strategy for treating this disease. The most developed method for targeting Aβ is the use of monoclonal antibodies including bapineuzumab, solanezumab and crenezumab. We have synthesized these antibodies and used surface(More)
Pyroglutamate-modified amyloid-β (pE-Aβ) is a highly neurotoxic amyloid-β (Aβ) isoform and is enriched in the brains of individuals with Alzheimer disease compared with healthy aged controls. Pyroglutamate formation increases the rate of Aβ oligomerization and alters the interactions of Aβ with Cu(2+) and lipids; however, a link between these properties and(More)
engagement with brain Aβ, consistent with published clinical data”. To reiterate, we reported data showing that bapineuzumab was capable of binding soluble Aβ with a low nanomolar affinity and demonstrated that the antibody could detect Aβ species in buffer and in brain homogenate and plasma from transgenic animal models of AD. Furthermore, in agreement(More)
There is a great interest in the role of free radicals and oxidative stress in Alzheimer's disease and for the role of transition metals in the generation of oligomers of Aβ peptides. In the literature, there are a multitude of varying methods that can be used to create soluble oligomers of Aβ, however, the processes that create these oligomers are often(More)
Elevated iron and decreased copper levels are cardinal features of the degenerating substantia nigra pars compacta in the Parkinson's disease brain. Both of these redox-active metals, and fellow transition metals manganese and zinc, are found at high concentrations within the midbrain and participate in a range of unique biological reactions. We examined(More)
IV. A novel and simple fluorescence method for the measurement of presynaptic vesicular zinc release in acute hippocampal slices with a fluorescence plate reader. II. Membrane-lipid therapy in operation: the Hsp co-inducer BGP-15 activates stress signal transduction pathways by remodeling plasma membrane rafts. III. Hydroximic acid derivatives: pleiotrophic(More)