Attenuated amyloid-beta aggregation and neurotoxicity owing to methionine oxidation.

Aggregation of the amyloid-beta (Abeta) peptide into amyloid plaques is a characteristic feature of Alzheimer's disease neuropathogenesis. We and others have previously demonstrated delayed Abeta aggregation as a consequence of oxidizing a single methionine residue at position 35 (Met-35). Here, we examined the consequences of Met-35 oxidation on the extremely aggregation-prone peptides Abeta1-42 and Abeta1-40Arctic with respect to protofibril and oligomer formation as well as neurotoxicity.

Cystatin C reduces the in vitro formation of soluble Abeta1-42 oligomers and protofibrils.

There are an increasing number of genetic and neuropathological observations to suggest that cystatin C, an extracellular protein produced by all nucleated cells, might play a role in the pathophysiology of sporadic Alzheimer's disease (AD). Recent observations indicate that small and large soluble oligomers of the beta-amyloid protein (Abeta) impair synaptic plasticity and induce neurotoxicity in AD. The objective of the present study was to investigate the influence of cystatin C on the production of such oligomers in vitro.

Beta-amyloid protein structure determines the nature of cytokine release from rat microglia.

Activated microglia represent a major source of inflammatory factors in Alzheimer's disease and a possible source of cytotoxic factors. beta-Amyloid (Abeta) peptide, the predominant component in amyloid plaques, has been shown to activate microglia and stimulate their production of inflammatory factors. The present study was performed to analyze the responses of microglia to different forms of Abeta, with regard to release of the proinflammatory cytokines interleukin-1alpha (IL-1alpha), IL-1beta, tumor necrosis factor-alpha (TNF-alpha), IL-6, and interferon-gamma (IFN-gamma), as well as the IL-1 receptor antagonist (IL-1ra).

Unique physicochemical profile of beta-amyloid peptide variant Abeta1-40E22G protofibrils: conceivable neuropathogen in arctic mutant carriers.

A new early-onset form of Alzheimer's disease (AD) was described recently where a point mutation was discovered in codon 693 of the beta-amyloid (Abeta) precursor protein gene, the Arctic mutation. The mutation translates into a single amino acid substitution, glutamic acid-->glycine, in position 22 of the Abeta peptide. The mutation carriers have lower plasma levels of Abeta than normal, while in vitro studies show that Abeta1-40E22G protofibril formation is significantly enhanced.

Oxidation of methionine 35 attenuates formation of amyloid beta -peptide 1-40 oligomers.

Amyloid plaques formed by aggregation of the amyloid beta-peptide (Abeta) are an intrinsic component of Alzheimer disease pathogenesis. It has been suggested that oxidation of methionine 35 in Abeta has implications for Alzheimer disease, and it has been shown that oxidation of Met-35 significantly inhibits aggregation in vitro. In this study, the aggregational properties of Abeta-(1-40) before and after Met-35 oxidation were investigated using electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry.