CAuSe or Consequence amyloid pathology in Alzheimer's DiseasE

Research Environment funded by the Swedish Research Council VR

News and Open Positions

01 Jun 2020: Two PhD positions in Translational Neurochemistry out. We are looking for 2 PhD students to work within our Cascade network together with Lund Univ and University College London. Link to Application


The research environment is built on a collaboration between scientists in biophysical chemistry and neurochemistry located at Lund University and the University of Gothenburg.

Emma Sparr, Physical Chemistry, Lund University
Jörg Hanrieder, Analytical Neurochemistry, University of Gothenburg
Sara Linse, Biochemistry, Lund University
Henrik Zetterberg, Clinical Neurochemistry, University of Gothenburg

The CASCADE research consortium builds on a number of key questions that can only be addressed through cross-disciplinary efforts. It is important to highlight that these questions are of high scientific interest from the perspectives of all participating scientists, meaning that the project is built on common drives to find an answer to these questions. The research team behind this application comes from strong cultures of collaboration; all have experience of working together with scientists from other fields with the ability and intension to work towards a common goal.

Research Summary

The molecular events leading to Alzheimer’s disease (AD) are largely unknown, in spite of this being one of the most examined questions in modern biomolecular research. This means that new angles are needed. Here we propose one new approach rooted in a physicochemical and molecular framework considering protein solubility, solubilization and modification, as well as protein-lipid interactions, which we place in context together with molecular neurochemistry insights on in vivo aggregation dynamics, plaque maturation and synaptic changes upon disease progress.

The goal is to answer the following scientific questions:

1) Is decreased solubility of amyloid β (Aβ) peptide a cause or a consequence of AD?

2) Is the gain of Aβ toxicity in AD caused by changes in the composition and molecular environment of structurally distinct amyloid plaques?

3) How does the structural conformation of Aβ aggregates relate to Aβ toxicity?

These questions are addressed through a concertated research effort involving advanced in vitro and in situ experiments using state of the technologies, including imaging mass spectrometry and solid-state NMR. 

We combine top-down and bottom-up approaches to study molecular mechanisms behind amyloid composition, deposition and toxicity, which processes are a cause or consequence of the pathophysiological changes during AD onset and progression. This requires studies of relevant biological samples with complex composition as well as model systems with well-defined compositions.