Alzheimer trigger discovered
Beta-amyloid fibrils extracted from human tissue

Ulm University

Researchers from Ulm University have been successful in isolating and examining amyloid fibrils from the human brain for the first time. These protein fibres are suspected of being in part responsible for triggering Alzheimer’s disease and cerebral amyloid angiopathy. Researchers from Ulm, Tübingen, Halle and San Diego worked together on this study, which was published in the journal Nature Communications.

Scientist have known for years that Alzheimer’s disease is connected to protein deposits in the brain. Among Alzheimer’s researchers, two proteins are considered to be particularly responsible for the disease: tau and beta-amyloids. These proteins form long molecules, so-called fibrils, which collect in the brain as fibre clumps. It is not yet known why the body’s own proteins become pathological and lead to degenerative changes in the brain.

Researchers from Ulm University have now been successful in extracting beta-amyloid fibrils from tissue samples of diseased brains and displaying them with precise detail. What is surprising is that the fibres markedly differ from the synthetically produced fibrils used for research purposes up to now. “Our main achievement thus far has been in making the structure of beta-amyloids visible, and demonstrating that they fundamentally differ from all previous assumptions”, explains Professor Marcus Fändrich, head of the Institute of Protein Biochemistry at Ulm University. For one thing, the individual peptides that make up the fibrils are formed differently than the test tube samples. What’s more, the fibrils under investigation are twisted in a completely different way than the synthetic samples. “This is a fundamentally different and completely unexpected characteristic”, Fändrich relates.

Extracting the amyloid fibrils from the tissue and then purifying them proved challenging

For their study, the researchers examined tissue samples taken from three patients and displaying the same structures. More than four years of intense work preceded their current findings. First, the scientists from Ulm, Tübingen, Halle (Saale) and San Diego were presented with the challenge of extracting the beta-amyloid fibrils from the tissue samples and then purifying them in a series of elaborate steps. When viewed under a cryo-electron microscope, the fibrils displayed numerous varying sub-types, further complicating the analysis.

The researchers from Ulm have thus quite possibly come one step closer to deciphering the causes of Alzheimer’s disease. One of the disease-causing structures, which is able to absorb beta-amyloid in the brain, is now known in much greater detail. “Scientists will now need to identify conditions that will produce these same structures in a test tube setting”, explains Fändrich. Further studies may be conducted on the basis of these beta-amyloid structures as well. It also has yet to be seen whether the new findings on beta-amyloid structure can be of use in developing pharmaceutical agents. The latest news from Ulm has already caused a considerable stir among experts.

Cryo-EM structure and polymorphism of Aβ amyloid fibrils purified from Alzheimer’s brain tissue. Marius Kollmer, William Close, Leonie Funk, Jay Rasmussen, Aref Bsoul, Angelika Schierhorn, Matthias Schmidt, Christina J. Sigurdson, Mathias Jucker & Marcus Fändrich; Nature Communications volume 10, Article number: 4760 (2019), published 29 October 2019,

Text: Jens Eber

Mediacontact: Andrea Weber-Tuckermann

Cryo-electron microscopic images of Aß amyloid fibrils
Cryo-electron microscopic images of Aß amyloid fibrils from the brain tissue of Alzehimer’s patients. Individual fibrils with different forms are highlighted (morphology I and II); © "Kollmer et al., Nature Communications"
Side-view of an Aß amyloid fibril
Side-view of an Aß amyloid fibril (left), cross-section of a fibril layer (upper center). The whole fibril consists of several stacked layers (lower right); © "Kollmer et al., Nature Communications"
Primary author Marius Kollmer with Prof Marcus Fändrich, head of the Institute of Protein Biochemistry