Structure of unmodified and pyroglutamylated amyloid beta peptides in lipid membranes

Alzheimer’s disease (AD) is a neurodegenerative disorder that causes brain atrophy, neuronal and synaptic loss, cognitive decline, and death. Worldwide, over 30 million people suffer from AD. Despite extensive basic and clinical research and multibillion investments in pharmaceutical efforts, no disease-modifying drugs are available for AD. One of the roadblocks in AD drug development is the incomplete understanding of molecular mechanisms underlying the disease. A major histopathological trait of AD is extracellular deposition of amyloid-beta (Aβ) peptide in brain parenchyma and vasculature, but the most toxic species are the intracellular oligomeric forms of Aβ.