@article {2019|2106, title = {Tetrameric Aβ40 and Aβ42 β-Barrel Structures by Extensive Atomistic Simulations. I. In a Bilayer Mimicking a Neuronal Membrane.}, journal = {J Phys Chem B}, volume = {123}, year = {2019}, month = {2019 May 02}, pages = {3643-3648}, abstract = {

The amyloid-β (Aβ) 42 oligomers are much more toxic than Aβ40 oligomers in Alzheimer\&$\#$39;s disease. Numerous experiments indicate that toxicity could involve the formation of pores in membranes, but experimental high-resolution structure determination of these pore-forming Aβ oligomers has been impeded by aggregate heterogeneity. Using extensive atomistic simulations, low-resolution data obtained in lipid bilayers, and other theoretical factors, we proposed atomic structures of Aβ40 and Aβ42 β-barrels in a bilayer mimicking a neuronal membrane. The 3D model, which consists of tetramer subunits, two distinct β-hairpin motifs and an asymmetric arrangement of eight antiparallel β-strands, is drastically destabilized for Aβ40 compared to its Aβ42 counterpart. Our computational modeling has several implications in Alzheimer\&$\#$39;s disease, sheds light on the amyloid pore hypothesis, and explains the higher deleterious property of Aβ42.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.9b01206}, author = {Phuong Hoang Nguyen and Campanera, Josep M and Ngo, Son Tung and Loquet, Antoine and Philippe Derreumaux} }