Space-based experiment opens new avenues in Alzheimer’s research — First structural analysis of Tottori-type amyloid β fibrils conducted in microgravity —

A collaborative team of researchers from the Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, Nagoya City University, Nagoya University, Japan Aerospace Exploration Agency (JAXA), and Japan Space Forum has succeeded in revealing the high-resolution structures of amyloid β (Aβ40) fibrils carrying the Tottori-type familial mutation (D7N) by leveraging the microgravity environment aboard the International Space Station’s “Kibo” module.

The D7N mutation, located in the N-terminal region of the Aβ peptide, is associated with rare familial cases of Alzheimer’s disease in Japan. On Earth, this variant predominantly forms amorphous non-fibrillar aggregates, which obstruct structural analysis. In contrast, the microgravity environment significantly suppressed these off-pathway aggregates, enabling the formation of well-ordered fibrils amenable to cryo-electron microscopy structural analysis.

Under microgravity, the team uncovered previously unobservable fibril architectures that do not form under ground-based conditions. The structural data indicate that the D7N mutation disrupts stabilizing interactions at the N-terminus, promoting alternative aggregation pathways that may be relevant to disease progression.

This achievement highlights how microgravity provides an ideal setting for investigating the intrinsic self-assembly behavior of amyloidogenic proteins by eliminating convection and sedimentation. In addition to advancing our understanding of Alzheimer’s disease mechanisms, the study demonstrates the powerful role of structural biology in space in overcoming long-standing limitations of Earth-based experiments.