Distinguished iNANO Lecture: The Role of Extrinsic and Intrinsic Factors in Amyloid β Peptide Aggregation

Dr. Sara Snogerup Linse
Professor of Physical Chemistry and Molecular Protein Science
Lund University, Dept of Biochemistry

The Role of Extrinsic and Intrinsic Factors in Amyloid β Peptide Aggregation

Sequence variants and environmental factors are crucial molecular determinants of the aggregation rate and mechanism of amyloid-β peptide (Aβ) implicated in Alzheimer's disease. We investigate these factors through highly reproducible experiments and global kinetic analyses. Examples of sequence modifications we have studied are truncations and extensions, as well as designed and disease-associated mutations. Examples of extrinsic factors we have studied are salt, pH, inhibitors and body fluids. Through these studies we learn not only about the role of each factor, but the results obtained under perturbations provide new insights also into the aggregation mechanism of the non-disturbed system. In several systems, we have investigated the possible co-aggregation of peptide variants as stimulated by the co-existence in humans of multiple Aβ sequence variants. Finally, detailed knowledge of the aggregation mechanism has enabled a search for cellular targets of transient oligomers on-pathway in the aggregation process.

Host: Associate professor Frans Mulder, iNANO & Department of Chemistry, Aarhus University