08.09.17 10:36

Research

Resarchers took Sharpest Image of Alzheimer’s Fibrils to Date

By: Redaktion/J. K.

A team of researchers from Germany and the Netherlands have determined the structure of an amyloid fibril with previously unachieved resolution. The atomic-level three-dimensional structure elucidated by scientists from Forschungszentrum Jülich, Heinrich Heine University Düsseldorf (HHU), the Centre for Structural Systems Biology in Hamburg, and Maastricht University displays previously unknown structural details which can answer many questions on the growth of harmful deposits and also explain the effect of genetic risk factors. The results have been published in the journal Science.

Cross section through the fibril illustrating the stepwise overlapping arrangement of the Aβ proteins. (Picture by Forschungszentrum Jülich / HHU / Gunnar Schröder)

Cross section through the fibril illustrating the stepwise overlapping arrangement of the Aβ proteins. (Picture by Forschungszentrum Jülich / HHU / Gunnar Schröder)

The structure reveals how the many single Aβ protein molecules are staggered in layers on top of each other and are arranged into so-called protofilaments. Two of these protofilaments are twinned around each other to form a fibril. If several of these fibrils become entangled, then this gives rise to the typical deposits or plaques that are detected in the brain tissues of Alzheimer’s patients.

The resolution of 4 angstroms, corresponding to 0.4 nanometres, achieved by the team is within the typical magnitude of atomic radii and atomic bond lengths. In contrast to previous work, the model shows for the first time the exact position and interactions of the proteins. Furthermore, the structure elucidates the location and conformation of all 42 amino acid residues of the many individual Aβ protein molecules for the first time.

This novel and detailed structure provides a new basis for understanding the structural effect of a number of genetic modifications that increase the risk of developing the disease. They stabilize the fibrils – as can now be seen – by changing the blueprint of the protein at defined locations. This e.g. also explains why in nature mice do not develop Alzheimer’s and why a small section of the Icelandic population seems to be more or less resistant to the disease. Their variants of Aβ differ by three or one amino acid residues, respectively, which are apparently important for the stability of the fibrils.

The results have been published on September 7th 2017 in the journal Science.

Further information

Contacts:

Dr. Lothar Gremer

Institute of Physical Biology at Heinrich Heine University Düsseldorf and Institute of Complex Systems (ICS-6), Forschungszentrum Jülich
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Jun.-Prof. Gunnar Schröder
Physics Department at Heinrich Heine University Düsseldorf and Institute of Complex Systems (ICS-6), Forschungszentrum Jülich
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Prof. Dieter Willbold
Institute of Physical Biology at Heinrich Heine University Düsseldorf and Institute of Complex Systems (ICS-6), Forschungszentrum Jülich
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Prof. Henrike Heise
Institute of Physical Biology at Heinrich Heine University Düsseldorf and Institute of Complex Systems (ICS-6), Forschungszentrum Jülich
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The article is available from science.sciencemag.org/lookup/doi/10.1126/science.aao2825 in English. The citation data and abstract are available free of charge from the same link; access to the full text may require a subscription.

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