Researchers in Switzerland have, for the first time, determined the three-dimensional structure of abnormal protein deposits linked to a rare and aggressive disease using a skin biopsy taken from a living patient, a breakthrough that could enable earlier and less invasive diagnosis.
The study, published in Nature Communications, focuses on transthyretin amyloidosis, or ATTR, a rare inherited or acquired condition caused by the misfolding of the transthyretin protein. The abnormal protein forms toxic amyloid deposits that accumulate in organs including the heart, nervous system, kidneys and eyes, leading to progressive organ failure.
Scientists from the University of Geneva and the Università della Svizzera Italiana said the findings mark a major shift in how the disease can be studied. Until now, structural analyses of amyloid fibrils were largely limited to tissue collected after a patient’s death, offering insight only into the disease’s final stages.
“This changes how we can understand the disease and evaluate treatment effects,” said Andreas Boland, a professor of molecular and cellular biology at the University of Geneva and one of the study’s senior authors.
The research team successfully isolated amyloid fibrils from a small skin biopsy obtained through a quick and minimally invasive procedure. Despite the limited sample size, the material was sufficient to analyze the molecular composition of the deposits and determine their three-dimensional structure using cryo-electron microscopy, a technique that allows proteins to be observed in near-atomic detail.
The researchers found that amyloid fibrils from skin tissue closely matched those previously observed in harder-to-access organs, such as the heart and brain. This suggests that skin biopsies can reliably reflect disease processes occurring deeper in the body.
“The minimally invasive nature of the biopsy means we can now study how these fibrils evolve over time, at different disease stages or in response to treatment,” said Xuefeng Zhang, a postdoctoral researcher at the University of Geneva and co-first author of the study.
ATTR amyloidosis shares biological mechanisms with more common neurodegenerative disorders, including Alzheimer’s and Parkinson’s disease, which are also driven by the buildup of misfolded proteins.
Encouraged by the results, the researchers plan to apply the same approach to other neurodegenerative conditions. Boland said the ability to study protein deposits directly in living patients could greatly expand research that has traditionally relied on post-mortem samples and may eventually support more personalized treatment strategies.
