Time-Dependent DNA Condensation Induced by Amyloid β-Peptide

The major protein component of the amyloid deposition in Alzheimer’s disease is a 39–43 residue peptide, amyloid β (Aβ). Aβ is toxic to neurons, although the mechanism of neurodegeneration is uncertain. Evidence exists for non-B DNA conformation in the hippocampus of Alzheimer’s disease brains, and Aβ was reportedly able to transform DNA conformation in vitro. In this study, we found that DNA conformation was altered in the presence of Aβ, and Aβ induced DNA condensation in a time-dependent manner. Furthermore, Aβ sheets, serving as condensation nuclei, were crucial for DNA condensation, and Cu2+ and Zn2+ ions inhibited Aβ sheet-induced DNA condensation. Our results suggest DNA condensation as a mechanism of Aβ toxicity.