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ERC

MAMBA Report Summary

Project ID: 340890
Funded under: FP7-IDEAS-ERC
Country: Sweden

Mid-Term Report Summary - MAMBA (Molecular mechanism of amyloid β aggregation)

We have found a mechanism that is compatible with all data for the self assembly of amyloid beta peptide (Abeta) from Alzheimers disease. The mechanism we find include three steps. The first step is called primary nucleation, this is like when dissolved gas in a liquid comes together to form the first small bubble. In the case of Abeta this is when two monomers come together in solution to form an aggregate which is stable enough that it grows faster by monomer addition than it dissociates back to two monomers. The second step is elongation, by which aggregates grow by monomer addition. This is like when you add to a pre-existing queue outside a restaurant. You feel less resistance to add to an existing queue than to enter an empty restaurant. For Abeta, the energy barrier towards elongation is much lower than for primary nucleation. The third step is secondary nucleation of monomers on fibril surface. this is when people for a secondary queue at the side of the previous one and this new queue budds off to go to a new restaurant. We have moreover found a number of factors that affect the self-assembly of Abeta and manage to reolve their effects over these three steps. We have investigated both intrinsic factors (properties of Abeta) and extrinsic factors (properties of the surrounding). Besides providing fundamental information on the self-assembly process of abeta, our results may contribute towards future treatment of Alzheimers disease.

Reported by

LUNDS UNIVERSITET
Sweden
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