In vitro reconstitution demonstrates the amyloid-beta mediated myelin membrane deformation [article]

Mohammed Saleem, Anuj Tiwari, Sweta Pradhan, Achinta Sannigrahi, Suman Jha, Krishnananda Chattopadhyay, Mithun Biswas
2021 bioRxiv   pre-print
Amyloid-beta (Ab) aggregation mediated neuronal membrane deformation, although poorly understood, is implicated in Alzheimer's Disease (AD). Particularly, whether Ab aggregation can induce neuronal demyelination remains unknown. Here we show that Aβ-40 binds and induces extensive tubulation in the myelin membrane in vitro. The binding of Aβ-40 depends predominantly on the lipid packing defect densities and electrostatic interactions and results in rigidification of the myelin membrane in the
more » ... ly time scales. Furthermore, elongation of Aβ-40 into higher oligomeric and fibrillar species leads to eventual fluidization of the myelin membrane followed by extensive membrane tubulation observed in the late phase. Taken together, our results capture mechanistic insights into snapshots of temporal dynamics of Aβ-40- myelin membrane interaction and demonstrate how short timescale, local phenomena of binding, and fibril mediated load generation manifests into long timescale, global phenomena of myelin tubulation and demonstrates the ability of Aβ-40 to demyelinate.
doi:10.1101/2021.08.13.456302 fatcat:hb3jk3nsgbebxn52ndgeacwdwq