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Updated: May 26, 2026

Biochemical Purification and Proteomic Characterization of Amyloid Fibril Cores from the Brain
Published on: April 28, 2022
Transthyretin amyloid fibrils adopt distinct folds in the brain
Shumaila Afrin1, Binh An Nguyen1, Parker Bassett1
1Center for Alzheimer's and Neurodegenerative Diseases, Department of Biophysics, Peter O'Donnell Jr Brain Institute, University of Texas Southwestern Medical Center (UTSW), Dallas, TX, USA.
Abstract:
Amyloid deposition in the central nervous system is increasingly recognized in transthyretin (ATTR) amyloidosis, particularly in patients with prolonged survival following liver transplantation or disease-modifying therapies. However, the structural basis of transthyretin aggregation in the brain remains unknown. Here we determine cryo-electron microscopy (cryo-EM) structures of ex vivo brain-derived ATTR fibrils from patients carrying the ATTRv-V30M and ATTRv-V30G variants. Both fibrils adopt folds distinct from those previously reported in peripheral tissues and the vitreous humor. V30M fibrils exhibit a continuous ordered core spanning residues Pro11-Asn124, whereas V30G fibrils consist of a substantially reduced ordered core, revealing pronounced structural divergence even within the same tissue environment. Despite this diversity, comparative analyses identify conserved regions across ATTR fibrils, including a segment implicated in transthyretin aggregation and targeted for diagnostic and therapeutic development. These results provide direct evidence that local tissue context can shape amyloid fibril architecture in human disease.
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