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A team of scientists from the Swiss Federal Institute of Technology in Lausanne (EPFL) and collaborators from the University of Ulm in Germany, the University of Modena and the University of Reggio Emilia in Italy, and the Massachusetts Institute of Technology have developed custom nanoparticles for high-resolution detection of amyloid fibrils, which are related to Alzheimer’s disease and Parkinson’s disease. The newly developed technology helps researchers to study specific fibril structures in amyloid diseases patients, allowing rapid and high-resolution imaging of fibrils. This breakthrough paper was published in PNAS onMarch 24, 2021, titled Unraveling the complexity of amyloid polymorphism using gold nanoparticles and cryo-EM.
One of the characteristics of Alzheimer’s disease is the presence of nodular structures between brain cells, which are called amyloid fibrils. These are formed from the notorious amyloid beta peptide and Tau protein, which are two of the most sought-after targets in the development of therapies for the treatment of Alzheimer’s and similar diseases. Beta amyloid and Tau protein are usually produced in the brain. However, these proteins can begin to entangle with each other, forming a huge fibril structure. When this happens, they can cause diseases such as Alzheimer’s disease and other neurodegenerative diseases.
Increasing evidence suggests that amyloid polymorphism gives rise to different strains of amyloids with distinct toxicities and pathology-spreading properties. Validating this hypothesis is challenging due to a lack of tools and methods that allow for the direct characterization of amyloid polymorphism in hydrated and complex biological samples. In this study, the research team describes nanoparticles (NPs) that efficiently label amyloid fibrils produced in vitro or isolated from postmortem tissues, under hydrating conditions and in such a way as to unmask their polymorphism and morphological features. Using these NPs, the researchers show that pathological aggregates exhibit exceptional morphological homogeneity compared with amyloid fibrils produced in vitro, consistent with the emerging view that the physiologic milieu is a key determinant of amyloid fibril strains.
These finding results should not only facilitate the profiling and characterization of amyloids for structural studies by cryo-EM, but also pave the way to elucidate the structural basis of amyloid strains and toxicity, and possibly the correlation between the pathological and clinical heterogeneity of amyloid diseases. The team also expressed that the nanoparticles are powerful and desperately needed tools for rapid imaging and profiling of amyloid morphological polymorphism in different types of samples under cryo-conditions, especially complex samples isolated from human-derived pathological aggregates.
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References
Cendrowska, U., Silva, P. J., Ait-Bouziad, N., Müller, M., Guven, Z. P., Vieweg, S., … & Lashuel, H. A. (2020). Unraveling the complexity of amyloid polymorphism using gold nanoparticles and cryo-EM. Proceedings of the National Academy of Sciences, 117(12), 6866-6874.
Ecole Polytechnique Fédérale de Lausanne. (2020, March 12). Gold nanoparticles uncover amyloid fibrils. ScienceDaily. Retrieved March 28, 2021.