| Title: |
Sensitivity and specificity of a seed amplification assay for diagnosis of multiple system atrophy: a multicentre cohort study |
| Authors: |
Ma Y.; Farris C. M.; Weber S.; Schade S.; Nguyen H.; Perez-Soriano A.; Giraldo D. M.; Fernandez M.; Soto M.; Camara A.; Painous C.; Munoz E.; Valldeoriola F.; Marti M. J.; Clarimon J.; Kallunki P.; Ma T. C.; Alcalay R. N.; Gomes B. F.; Blennow K.; Zetterberg H.; Constantinescu J.; Mengel D.; Kadam V.; Parchi P.; Brockmann K.; Tropea T. F.; Siderowf A.; Synofzik M.; Kang U. J.; Compta Y.; Svenningsson P.; Mollenhauer B.; Concha-Marambio L. |
| Contributors: |
Ma, Y.; Farris, C. M.; Weber, S.; Schade, S.; Nguyen, H.; Perez-Soriano, A.; Giraldo, D. M.; Fernandez, M.; Soto, M.; Camara, A.; Painous, C.; Munoz, E.; Valldeoriola, F.; Marti, M. J.; Clarimon, J.; Kallunki, P.; Ma, T. C.; Alcalay, R. N.; Gomes, B. F.; Blennow, K.; Zetterberg, H.; Constantinescu, J.; Mengel, D.; Kadam, V.; Parchi, P.; Brockmann, K.; Tropea, T. F.; Siderowf, A.; Synofzik, M.; Kang, U. J.; Compta, Y.; Svenningsson, P.; Mollenhauer, B.; Concha-Marambio, L. |
| Publication Year: |
2024 |
| Collection: |
IRIS Università degli Studi di Bologna (CRIS - Current Research Information System) |
| Subject Terms: |
RT-QuIC; Seed Amplification Assay (SAA); alpha-synuclein; MSA; Biomarker |
| Description: |
Background: The pathological hallmarks of multiple system atrophy and Parkinson's disease are, respectively, misfolded-α-synuclein-laden glial cytoplasmic inclusions and Lewy bodies. CSF-soluble misfolded α-synuclein aggregates (seeds) are readily detected in people with Parkinson's disease by α-synuclein seed amplification assay (synSAA), but identification of seeds associated with multiple system atrophy for diagnostic purposes has proven elusive. We aimed to assess whether a novel synSAA could reliably distinguish seeds from Lewy bodies and glial cytoplasmic inclusions. Methods: In this multicentre cohort study, a novel synSAA that multiplies and detects seeds by fluorescence was used to analyse masked CSF and brain samples from participants with either clinically diagnosed or pathology-confirmed multiple system atrophy, Parkinson's disease, dementia with Lewy bodies, isolated rapid eye movement sleep behaviour disorder (IRBD), disorders that were not synucleinopathies, or healthy controls. Participants were from eight available cohorts from seven medical centres in four countries: New York Brain Bank, New York, USA (NYBB); University of Pennsylvania, Philadelphia, PA, USA (UPENN); Paracelsus-Elena-Klinik, Kassel, Germany (DeNoPa and KAMSA); Hospital Clinic Barcelona, Spain (BARMSA); Universität Tübingen, Tübingen, Germany (EKUT); Göteborgs Universitet, Göteborgs, Sweden (UGOT); and Karolinska Institutet, Stockholm, Sweden (KIMSA). Clinical cohorts were classified for expected diagnostic accuracy as either research (longitudinal follow-up visits) or real-life (single visit). Sensitivity and specificity were estimated according to pathological (gold standard) and clinical (reference standard) diagnoses. Findings: In 23 brain samples (from the NYBB cohort), those containing Lewy bodies were synSAA-positive and produced high fluorescence amplification patterns (defined as type 1); those containing glial cytoplasmic inclusions were synSAA-positive and produced intermediate fluorescence (defined as type 2); ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
STAMPA |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/39577923; info:eu-repo/semantics/altIdentifier/wos/WOS:001412281400001; volume:23; issue:12; firstpage:1225; lastpage:1237; numberofpages:13; journal:LANCET NEUROLOGY; https://hdl.handle.net/11585/1007483 |
| DOI: |
10.1016/S1474-4422(24)00395-8 |
| Availability: |
https://hdl.handle.net/11585/1007483; https://doi.org/10.1016/S1474-4422(24)00395-8 |
| Accession Number: |
edsbas.467F772D |
| Database: |
BASE |