α-Synuclein Pathology in PRKN-Linked Parkinson's Disease: New Insights from a Blood-Based Seed Amplification Assay.
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
28 Mar 2024
28 Mar 2024
Historique:
revised:
04
03
2024
received:
25
10
2023
accepted:
06
03
2024
medline:
28
3
2024
pubmed:
28
3
2024
entrez:
28
3
2024
Statut:
aheadofprint
Résumé
Pathogenic variants in PRKN cause early-onset Parkinson's disease (PD), while the role of alpha-synuclein in PRKN-PD remains uncertain. One study performed a blood-based alpha-synuclein seed amplification assay (SAA) in PRKN-PD, not detecting seed amplification in 17 PRKN-PD patients. By applying a methodologically different SAA focusing on neuron-derived extracellular vesicles, we demonstrated alpha-synuclein seed amplification in 8 of 13 PRKN-PD patients, challenging the view of PRKN-PD as a non-synucleinopathy. Moreover, we performed blinded replication of the neuron-derived extracellular vesicles-dependent SAA in idiopathic PD patients and healthy controls. In conclusion, blood-based neuron-derived extracellular vesicles-dependent SAA represents a promising biomarker to elucidate the underpinnings of (monogenic) PD. ANN NEUROL 2024.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : EU Joint Programme - Neurodegenerative Disease Research
Organisme : Deutsche Forschungsgemeinschaft
ID : FOR2488
Organisme : Michael J. Fox Foundation for Parkinson's Research
Organisme : Else Kröner-Fresenius-Stiftung
Organisme : Horizon 2020 Framework Programme
ID : 668738
Informations de copyright
© 2024 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
Références
Wasner K, Grünewald A, Klein C. Parkin‐linked Parkinson's disease: from clinical insights to pathogenic mechanisms and novel therapeutic approaches. Neurosci Res 2020;159:34–39.
Dickson DW, Braak H, Duda JE, et al. Neuropathological assessment of Parkinson's disease: refining the diagnostic criteria. Lancet Neurol 2009;8:1150–1157.
Gelb DJ, Oliver E, Gilman S. Diagnostic criteria for Parkinson disease. Arch Neurol 1999;56:33–39.
Fairfoul G, McGuire LI, Pal S, et al. Alpha‐synuclein RT‐QuIC in the CSF of patients with alpha‐synucleinopathies. Ann Clin Transl Neurol 2016;3:812–818.
Shahnawaz M, Tokuda T, Waragai M, et al. Development of a biochemical diagnosis of Parkinson disease by detection of α‐Synuclein misfolded aggregates in cerebrospinal fluid. JAMA Neurol 2017;74:163–172.
Rossi M, Candelise N, Baiardi S, et al. Ultrasensitive RT‐QuIC assay with high sensitivity and specificity for Lewy body‐associated synucleinopathies. Acta Neuropathol 2020;140:49–62.
Iranzo A, Fairfoul G, Ayudhaya ACN, et al. Detection of α‐synuclein in CSF by RT‐QuIC in patients with isolated rapid‐eye‐movement sleep behaviour disorder: a longitudinal observational study. Lancet Neurol 2021;20:203–212.
Siderowf A, Concha‐Marambio L, Lafontant D‐E, et al. Assessment of heterogeneity among participants in the Parkinson's progression markers initiative cohort using α‐synuclein seed amplification: a cross‐sectional study. Lancet Neurol 2023;22:407–417.
Kluge A, Bunk J, Schaeffer E, et al. Detection of neuron‐derived pathological α‐synuclein in blood. Brain 2022;145:3058–3071.
Okuzumi A, Hatano T, Matsumoto G, et al. Propagative α‐synuclein seeds as serum biomarkers for synucleinopathies. Nat Med 2023;29:1448–1455.
Pramstaller PP, Schlossmacher MG, Jacques TS, et al. Lewy body Parkinson's disease in a large pedigree with 77 Parkin mutation carriers. Ann Neurol 2005;58:411–422.
Lobanova E, Whiten D, Ruggeri FS, et al. Imaging protein aggregates in the serum and cerebrospinal fluid in Parkinson's disease. Brain 2022;145:632–643.
Candelise N, Schmitz M, Llorens F, et al. Seeding variability of different alpha synuclein strains in synucleinopathies. Ann Neurol 2019;85:691–703.
Madsen DA, Schmidt SI, Blaabjerg M, Meyer M. Interaction between Parkin and α‐Synuclein in PARK2‐mediated Parkinson's disease. Cells 2021;10:283.
Schneider SA, Alcalay RN. Neuropathology of genetic synucleinopathies with parkinsonism: review of the literature. Mov Disord 2017;32:1504–1523.
Chung KK, Zhang Y, Lim KL, et al. Parkin ubiquitinates the alpha‐synuclein‐interacting protein, synphilin‐1: implications for Lewy‐body formation in Parkinson disease. Nat Med 2001;7:1144–1150.
Ma L‐Y, Liu G‐L, Wang D‐X, et al. Alpha‐Synuclein in peripheral tissues in Parkinson's disease. ACS Chem Nerosci 2019;10:812–823.
Shin JH, Park S‐H, Shin C, et al. Negative α‐synuclein pathology in the submandibular gland of patients carrying PRKN pathogenic variants. Parkinsonism Relat Disord 2020;81:179–182.