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Lookup NU author(s): Professor Tiago OuteiroORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2026 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.Seed amplification assays (SAAs) enable ultrasensitive detection of misfolded α-synuclein across biofluids and tissues. Yet, heterogeneity in protocols limits cross-study comparability and clinical translation. Here, we review α-synuclein SAA methods and their performance across various biological matrices. We catalog key variables (e.g., human recombinant α-synuclein variants, buffers, salts, beads, shaking, incubation temperature) and outline pre-analytical factors that shape outcomes. We propose a prioritized framework of key analytical and pre-analytical variables most likely to influence assay reproducibility and clinical interpretation. We also outline minimal reporting criteria and practical quality-control checkpoints, and recommend multicenter interlaboratory proficiency testing as essential steps to accelerate the robust clinical and research implementation of α-synuclein SAAs.
Author(s): Amaral-do-Nascimento M, Santos DF, Vieira TCRG, Outeiro TF
Publication type: Review
Publication status: Published
Journal: Annals of Clinical and Translational Neurology
Year: 2026
Pages: Epub ahead of print
Online publication date: 01/04/2026
Acceptance date: 13/03/2026
ISSN (print): 2328-9503
ISSN (electronic): 2328-9503
Publisher: John Wiley and Sons Inc
URL: https://doi.org/10.1002/acn3.70384
DOI: 10.1002/acn3.70384
Data Access Statement: This manuscript is a systematic review and synthesis of previously published studies. No new primary datasets were generated. All data supporting the findings of this review are available within the article and its Supporting Information and/or the cited literature.
