Abstract
The Radical Model of Alzheimer's Disease (AD) is presented in some detail. The model provides a unified picture for the role of the amyloid beta peptide (Aβ), Met35, copper ions, oxygen, beta sheet secondary structure, and the generation of hydrogen peroxide, in mediating oxidative stress in AD. It predicts a role for glycyl radicals as long-lived species which can transport the damage into cell membranes and initiate lipid peroxidation. Previous work has established the thermodynamic and kinetic viability of most of the steps. In the present work, QM/MM and Amber calculations reveal that self assembly of antiparallel β-sheet which brings Met35 into the required close proximity to a glycine residue is more likely if the residue is Gly29 or Gly33, than any of the other four glycine residues of Aβ.
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