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Updated: Aug 9, 2026
09:06
Amyloid and the Cross-Beta Architecture
Published on: February 13, 2026
Polymorphic structures of rapidly twisting 40-residue amyloid-β fibrils
Motahareh G Larimi1, Kent R Thurber1, Robert Tycko1
1Laboratory of Chemical Physics National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda, MD 20892-0520.
Biophysical Journal
|August 8, 2026
Summary
Researchers used cryo-EM to study amyloid-beta 40 (Aβ40) fibrils, revealing three distinct structures with similar sizes but different molecular arrangements. This deepens understanding of amyloid polymorphism and its relation to Alzheimer's disease.
Area of Science:
- Biochemistry
- Structural Biology
- Neuroscience
Background:
- Amyloid-beta (Aβ) peptides, particularly Aβ40 and Aβ42, form polymorphic fibrils with structures sensitive to growth conditions.
- The structural variations in these fibrils are not fully understood, hindering insights into amyloid diseases.
Purpose of the Study:
- To characterize the high-resolution structures of rapidly twisting Aβ40 fibrils using cryogenic electron microscopy (cryo-EM).
- To investigate the structural diversity among Aβ40 polymorphs grown under identical conditions.
Main Methods:
- Utilized cryogenic electron microscopy (cryo-EM) to determine the structures of Aβ40 fibrils.
- Analyzed fibrils with an approximate cross-over distance of 25 nm.
Main Results:
- Identified three distinct rapidly twisting Aβ40 polymorphs from samples grown under a single set of conditions.
- These polymorphs exhibited variations in twist handedness, symmetry, molecular conformations, and intermolecular contacts despite similar cross-over distances.
- Two polymorphs showed similarities to previously described Aβ40 structures but possessed shorter ordered segments and other conformational differences.
Conclusions:
- The study reveals significant structural diversity within rapidly twisting Aβ40 fibrils, even under uniform growth conditions.
- Findings enhance the understanding of amyloid polymorphism and the relationship between fibril morphology and molecular structure.
- Provides insights into the structural connections between in vitro-generated and brain-derived amyloid fibrils relevant to Alzheimer's disease.
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