Determination of the Correlation between Conductance and Architecture of Disordered β-amyloid Channels

6 It has been hypothesized that the insertion of cation preferential channels into 7 neuronal cell membranes disrupts homeostasis and function leading to 8 Alzheimer’s disease. These channels have been shown to be composed of 9 variable numbers of subunits. The nonhomogenous configuration of these 10 subunits in the channels has introduced difficulties in defining set values of ion 11 conductance. Here we model β-amyloid (Aβ) channels as a cylinder spanning 12 the cell membrane of variable radius dependent on subunit configuration. 13 Various subunit motifs were examined and the expected conductance for each 14 configuration determined. The theoretically determined conductance was then 15 compared to experimentally observed values and a new mechanism for pore 16 growth through successive subunit addition is proposed. This work will allow 17 for the introduction of these channels into electrodynamic models of neurons to 18 illuminate the effects of channel insertion into the cell membrane and expand 19 our understanding of neurodegenerative diseases. 20