Structural evolution and membrane interactions of Alzheimer's amyloid-beta peptide oligomers: new knowledge from single-molecule fluorescence studies.

Amyloid-β peptide (Aβ) oligomers may represent the proximal neurotoxin in Alzheimer's disease. Single-molecule microscopy (SMM) techniques have recently emerged as a method for overcoming the innate difficulties of working with amyloid-β, including the peptide's low endogenous concentrations, the dynamic nature of its oligomeric states, and its heterogeneous and complex membrane interactions. SMM techniques have revealed that small oligomers of the peptide bind to model membranes and cells at low nanomolar-to-picomolar concentrations and diffuse at rates dependent on the membrane characteristics.

Single-molecule imaging reveals aβ42:aβ40 ratio-dependent oligomer growth on neuronal processes.

Soluble oligomers of the amyloid-β peptide have been implicated as proximal neurotoxins in Alzheimer's disease. However, the identity of the neurotoxic aggregate(s) and the mechanisms by which these species induce neuronal dysfunction remain uncertain. Physiologically relevant experimentation is hindered by the low endogenous concentrations of the peptide, the metastability of Aβ oligomers, and the wide range of observed interactions between Aβ and biological membranes.

The marketing of dissolvable tobacco: social science and public policy research needs.

The latest generation of smokeless tobacco products encompasses a wide range of offerings, including what is commonly referred to as dissolvable tobacco. Designed to deliver nicotine upon dissolving or disintegrating in a user's mouth, dissolvable tobacco products currently appear in various United States markets as strips, orbs, sticks, and lozenges. The emergence of these new products poses distinct opportunities and challenges for social and behavioral science and public health research and raises important public policy questions.

Direct observation of single amyloid-β(1-40) oligomers on live cells: binding and growth at physiological concentrations.

Understanding how amyloid-β peptide interacts with living cells on a molecular level is critical to development of targeted treatments for Alzheimer's disease. Evidence that oligomeric Aβ interacts with neuronal cell membranes has been provided, but the mechanism by which membrane binding occurs and the exact stoichiometry of the neurotoxic aggregates remain elusive. Physiologically relevant experimentation is hindered by the high Aβ concentrations required for most biochemical analyses, the metastable nature of Aβ aggregates, and the complex variety of Aβ species present under physiological conditions.