Lipid Fibrils: A New Building Block in Understanding Alzheimer’s
Lipids play a crucial role in the development of Alzheimer’s disease, but the details of this process were previously unknown. A team of scientists from Jülich from Helmholtz Information, Göttingen, and Düsseldorf has now determined the atomic structures of lipid-fibril complexes for the first time. They discovered entirely new fibril structures, as reported in the journal Nature Communications. (Source: Forschungszentrum Jülich – Press Releases)
The peptide Amyloid-beta plays a central role in Alzheimer’s disease, forming deposits in the diseased brain made up of fibrils: fiber-like structures composed of the peptide. It has long been known that lipids and lipid membranes must play a significant role in the formation of these Amyloid-beta deposits. However, it was not known how exactly lipids interact with Amyloid-beta fibrils.
Scientific Result
Cryo-electron microscopy (Cryo-EM), a type of transmission electron microscopy where biological samples are examined at very low temperatures, was utilized. With this technique, in combination with NMR spectroscopy and molecular modeling, the scientists were able to show for the first time how lipids bind to the Amyloid-beta fibrils and interfere in fibril formation.
Cryo-EM makes the structures of the fibril-lipid complexes visible with atomic resolution. This provides important insights into the fundamentals and development of Alzheimer’s disease. The team from the Jülich Research Center, the Max Planck Institute (MPI) for Multidisciplinary Sciences, and Heinrich Heine University Düsseldorf (HHU) also found several new fibril structures, which are stable solely through binding to the lipids.
Societal and Scientific Relevance
These new findings provide important explanations for the development of Alzheimer’s disease. They allow for a better understanding of how lipids bind to the fibrils and how they influence the formation of fibrils. “It appears that the fibrils can absorb a large amount of lipids,” explains Gunnar Schröder from the Jülich Institute for Biological Information Processes and HHU, one of the study’s corresponding authors. “This could support a commonly described theory about the toxicity of Amyloid-beta aggregation, suggesting that fibril formation destroys lipid membranes, thereby damaging nerve cells,” elucidates Max Planck group leader Loren Andreas.
“Although our structures were produced in a test tube,” says Gunnar Schröder, “they could provide clues about how Amyloid-beta peptides interact with the lipid membrane. This knowledge is another important component for the development of drugs against Alzheimer’s.”
Further Details
For their measurements, the scientists used NMR spectroscopy and cryo-electron microscopy. “Producing the Amyloid-beta peptide with the highest purity for Cryo-EM and NMR spectroscopy required years of developmental work,” says Stefan Becker from the MPI. In the Cryo-EM method, biological samples are flash-frozen ultrafast, putting them in an amorphous, glass-like state: existing water turns into amorphous ice, allowing complex protein structures to be analyzed. The data obtained were recorded at the MPI for Multidisciplinary Sciences in Göttingen.
FZJ/R. Panknin, 01.03.2024
Note: The article has been translated from German to English. It is based on a press release from the FZJ.
The original press release can be found at:
Lipidfibrillen: Ein neuer Baustein zum Verständnis von Alzheimer (only in german)
The original publication can be found at (Open Access):
Cryo-EM structures of lipidic fibrils of amyloid-β (1-40), Nature Communications, February 2024, by Benedikt Frieg Mookyoung Han, KarinGiller, Christian Dienemann, Dietmar Riedel, Stefan Becker, Loren B. Andreas, Christian Griesinger & Gunnar F. Schröder. DOI: 10.1038/s41467-023-43822-x
Localization in the Helmholtz Research Field Information:
Helmholtz Research Field Information, Program 2: Natural, Artificial and Cognitive Information Processing, Topic 4: Molecular and Cellular Information Processing
Further Information:
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Contact:
Prof. Dr. Gunnar Schröder
Institute of Biological Information Processing (IBI)
Structural Biochemistry (IBI-7)
Forschungszentrum Jülich
Tel.: +49 2461/61-3259
E-Mail: gu.schroeder@fz-juelich.de
Contact for this press release:
Dr. Regine Panknin
Press Officer
Forschungszentrum Jülich
Phone: +49 2461 61-9054
E-Mail: r.panknin@fz-juelich.de
