Pathological α-synuclein detected by real-time quaking-induced conversion in synucleinopathies

synucleinopathies are diseases characterized by the aggregation of α-synuclein (α-syn), which forms fibrils through misfolding and accumulates in a prion-like manner. To detect the presence of these α-syn aggregates in clinical samples, seed amplification assays (SAAs) have been developed. These SAA...

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Main Authors: Juan Huang, Xingxing Yuan, Lin Chen, Binbin Hu, Hui Wang, Ye Wang, Wei Huang
Format: Article
Language:English
Published: Elsevier 2024-03-01
Series:Experimental Gerontology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0531556524000081
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author Juan Huang
Xingxing Yuan
Lin Chen
Binbin Hu
Hui Wang
Ye Wang
Wei Huang
author_facet Juan Huang
Xingxing Yuan
Lin Chen
Binbin Hu
Hui Wang
Ye Wang
Wei Huang
author_sort Juan Huang
collection DOAJ
description synucleinopathies are diseases characterized by the aggregation of α-synuclein (α-syn), which forms fibrils through misfolding and accumulates in a prion-like manner. To detect the presence of these α-syn aggregates in clinical samples, seed amplification assays (SAAs) have been developed. These SAAs are capable of amplifying the α-syn seeds, allowing for their detection. αSyn-SAAs have been reported under the names ‘protein misfolding cyclic amplification’ (αSyn-PMCA) and ‘real-time quaking-induced conversion'α-Syn-RT-QuIC. The α-Syn RT-QuIC, in particular, has been adapted to amplify and detect α-syn aggregates in various biospecimens, including cerebrospinal fluid (CSF), skin, nasal brushing, serum and saliva. The α-syn RT-QuIC assay has demonstrated good sensitivity and specificity in detecting pathological α-syn, particularly in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) cases, with an accuracy rate of up to 80 %. Additionally, differential diagnosis between DLB and PD, as well as PD and multiple system atrophy (MSA), can be achieved by utilizing certain kinetic thioflavin T (ThT) parameters and other parameters. Moreover, the positive detection of α-syn in the prodromal stage of synucleinopathies provides an opportunity for early intervention and management. In summary, the development of the α-syn RT-QuIC assay has greatly contributed to the field of synucleinopathies. Therefore, we review the development of α-syn RT-QuIC assay and describe in detail the recent advancements of α-syn RT-QuIC assay for detecting pathological α-syn in synucleinopathies.
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spelling doaj.art-873b9d9fc51647a28a51c50358d164502024-02-25T04:34:43ZengElsevierExperimental Gerontology1873-68152024-03-01187112366Pathological α-synuclein detected by real-time quaking-induced conversion in synucleinopathiesJuan Huang0Xingxing Yuan1Lin Chen2Binbin Hu3Hui Wang4Ye Wang5Wei Huang6Department of Neurology, Second Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, ChinaDepartment of Anesthesiology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, ChinaDepartment of Neurology, Second Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, ChinaDepartment of Neurology, Second Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, ChinaDepartment of Neurology, Second Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, ChinaDepartment of Neurology, Second Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, China; Corresponding author.Department of Neurology, Second Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, China; Corresponding author.synucleinopathies are diseases characterized by the aggregation of α-synuclein (α-syn), which forms fibrils through misfolding and accumulates in a prion-like manner. To detect the presence of these α-syn aggregates in clinical samples, seed amplification assays (SAAs) have been developed. These SAAs are capable of amplifying the α-syn seeds, allowing for their detection. αSyn-SAAs have been reported under the names ‘protein misfolding cyclic amplification’ (αSyn-PMCA) and ‘real-time quaking-induced conversion'α-Syn-RT-QuIC. The α-Syn RT-QuIC, in particular, has been adapted to amplify and detect α-syn aggregates in various biospecimens, including cerebrospinal fluid (CSF), skin, nasal brushing, serum and saliva. The α-syn RT-QuIC assay has demonstrated good sensitivity and specificity in detecting pathological α-syn, particularly in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) cases, with an accuracy rate of up to 80 %. Additionally, differential diagnosis between DLB and PD, as well as PD and multiple system atrophy (MSA), can be achieved by utilizing certain kinetic thioflavin T (ThT) parameters and other parameters. Moreover, the positive detection of α-syn in the prodromal stage of synucleinopathies provides an opportunity for early intervention and management. In summary, the development of the α-syn RT-QuIC assay has greatly contributed to the field of synucleinopathies. Therefore, we review the development of α-syn RT-QuIC assay and describe in detail the recent advancements of α-syn RT-QuIC assay for detecting pathological α-syn in synucleinopathies.http://www.sciencedirect.com/science/article/pii/S0531556524000081Seed amplification assaysα-Syn RT-QuICSelf-propagationAggregated α-synucleinSynucleinopathies
spellingShingle Juan Huang
Xingxing Yuan
Lin Chen
Binbin Hu
Hui Wang
Ye Wang
Wei Huang
Pathological α-synuclein detected by real-time quaking-induced conversion in synucleinopathies
Experimental Gerontology
Seed amplification assays
α-Syn RT-QuIC
Self-propagation
Aggregated α-synuclein
Synucleinopathies
title Pathological α-synuclein detected by real-time quaking-induced conversion in synucleinopathies
title_full Pathological α-synuclein detected by real-time quaking-induced conversion in synucleinopathies
title_fullStr Pathological α-synuclein detected by real-time quaking-induced conversion in synucleinopathies
title_full_unstemmed Pathological α-synuclein detected by real-time quaking-induced conversion in synucleinopathies
title_short Pathological α-synuclein detected by real-time quaking-induced conversion in synucleinopathies
title_sort pathological α synuclein detected by real time quaking induced conversion in synucleinopathies
topic Seed amplification assays
α-Syn RT-QuIC
Self-propagation
Aggregated α-synuclein
Synucleinopathies
url http://www.sciencedirect.com/science/article/pii/S0531556524000081
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