Imaging Amyloid-β Membrane Interactions: Ion-Channel Pores and Lipid-Bilayer Permeability in Alzheimer's Disease.

The accumulation of the amyloid-β peptides (Aβ) is central to the development of Alzheimer's disease. The mechanism by which Aβ triggers a cascade of events that leads to dementia is a topic of intense investigation. Aβ self-associates into a series of complex assemblies with different structural and biophysical properties.

Copper(II) Can Kinetically Trap Arctic and Italian Amyloid-β as Toxic Oligomers, Mimicking Cu(II) Binding to Wild-Type Amyloid-β: Implications for Familial Alzheimer's Disease.

The self-association of amyloid-β (Aβ) peptide into neurotoxic oligomers is believed to be central to Alzheimer's disease (AD). Copper is known to impact Aβ assembly, while disrupted copper homeostasis impacts phenotype in Alzheimer's models. Here we show the presence of substoichiometric Cu(II) has very different impacts on the assembly of Aβ40 and Aβ42 isoforms.

Impact of Membrane Phospholipids and Exosomes on the Kinetics of Amyloid-β Fibril Assembly.

Alzheimer's disease (AD) is linked with the self-association of the amyloid-β peptide (Aβ) into oligomers and fibrils. The brain is a lipid rich environment for Aβ to assemble, while the brain membrane composition varies in an age dependent manner, we have therefore monitored the influence of lipid bilayer composition on the kinetics of Aβ40 fibril assembly. Using global-fitting models of fibril formation kinetics, we show that the microscopic rate constant for primary nucleation is influenced by variations in phospholipid composition.

Drosophila Models Reveal Properties of Mutant Lamins That Give Rise to Distinct Diseases.

Mutations in the gene cause a collection of diseases known as laminopathies, including muscular dystrophies, lipodystrophies, and early-onset aging syndromes. The gene encodes A-type lamins, lamins A/C, intermediate filaments that form a meshwork underlying the inner nuclear membrane. Lamins have a conserved domain structure consisting of a head, coiled-coil rod, and C-terminal tail domain possessing an Ig-like fold.

Imaging Amyloid-β Membrane Interactions: Ion-Channel Pores and Lipid-Bilayer Permeability in Alzheimer's Disease.

The accumulation of the amyloid-β peptides (Aβ) is central to the development of Alzheimer's disease. The mechanism by which Aβ triggers a cascade of events that leads to dementia is a topic of intense investigation. Aβ self-associates into a series of complex assemblies with different structural and biophysical properties.