eprintid: 10147819 rev_number: 12 eprint_status: archive userid: 699 dir: disk0/10/14/78/19 datestamp: 2022-05-05 10:48:28 lastmod: 2024-10-24 09:55:06 status_changed: 2022-05-05 10:48:28 type: article metadata_visibility: show sword_depositor: 699 creators_name: Garcia-Moreno, Hector creators_name: Prudencio, Mercedes creators_name: Thomas-Black, Gilbert creators_name: Solanky, Nita creators_name: Jansen-West, Karen R creators_name: Hanna Al-Shaikh, Rana creators_name: Heslegrave, Amanda creators_name: Zetterberg, Henrik creators_name: Santana, Magda M creators_name: Pereira de Almeida, Luis creators_name: Vasconcelos-Ferreira, Ana creators_name: Januário, Cristina creators_name: Infante, Jon creators_name: Faber, Jennifer creators_name: Klockgether, Thomas creators_name: Reetz, Kathrin creators_name: Raposo, Mafalda creators_name: Ferreira, Ana F creators_name: Lima, Manuela creators_name: Schöls, Ludger creators_name: Synofzik, Matthis creators_name: Hübener-Schmid, Jeannette creators_name: Puschmann, Andreas creators_name: Gorcenco, Sorina creators_name: Wszolek, Zbigniew K creators_name: Petrucelli, Leonard creators_name: Giunti, Paola title: Tau and neurofilament light-chain as fluid biomarkers in spinocerebellar ataxia type 3 ispublished: pub subjects: UCH divisions: C07 divisions: F86 divisions: B02 divisions: UCL divisions: D07 divisions: F84 keywords: Biomarkers, Cerebellum, Neurofilaments, Tau, Spinocerebellar ataxias note: Copyright © 2022 The Authors. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. abstract: BACKGROUND: Clinical trials in SCA3 will require biomarkers for use as outcome measures. METHODS: To evaluate total tau (t-tau), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCHL1), and neurofilament light-chain (NfL) as fluid biomarkers in SCA3, ATXN3 mutation carriers (n=143) and controls (n=172) were clinically assessed, and plasma concentrations of the four proteins were analysed on the Simoa HD-1 platform. Eleven ATXN3 mutation carrier CSF samples were analysed for t-tau and phosphorylated tau (p-tau181 ). A transgenic SCA3 mouse model (MJDTg) was used to measure cerebellar t-tau levels. RESULTS: Plasma t-tau levels were higher in mutation carriers below the age of 50, compared to controls, and the Inventory of Non-Ataxia Signs was associated with t-tau in ataxic patients (p=0.004). Preataxic carriers showed higher CSF t-tau and p-tau181 concentrations compared to ataxic patients (p=0.025 and p=0.014, respectively). Cerebellar t-tau was elevated in MJDTg mice compared to wild-type (p=0.033), only in early stages of the disease. GFAP and UCHL1 did not show higher levels in mutation carriers compared to controls. Plasma NfL concentrations were higher in mutation carriers compared to controls, and differences were greater for younger carriers. The Scale for the Assessment and Rating of Ataxia was the strongest predictor of NfL in ataxic patients (p<0.001). CONCLUSION: Our results suggest that tau might be a marker of early disease stages in SCA3. NfL can discriminate mutation carriers from controls and is associated to different clinical variables. Longitudinal studies are required to confirm their potential role as biomarkers in clinical trials. date: 2022-08 date_type: published official_url: https://doi.org/10.1111/ene.15373 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1952196 doi: 10.1111/ene.15373 medium: Print-Electronic lyricists_name: Zetterberg, Henrik lyricists_name: Giunti, Paola lyricists_name: Garcia Moreno, Hector lyricists_id: HZETT94 lyricists_id: PGIUN65 lyricists_id: HGARC46 actors_name: Flynn, Bernadette actors_id: BFFLY94 actors_role: owner full_text_status: public publication: European Journal of Neurology volume: 29 number: 8 pagerange: 2439-2452 event_location: England citation: Garcia-Moreno, Hector; Prudencio, Mercedes; Thomas-Black, Gilbert; Solanky, Nita; Jansen-West, Karen R; Hanna Al-Shaikh, Rana; Heslegrave, Amanda; ... Giunti, Paola; + view all <#> Garcia-Moreno, Hector; Prudencio, Mercedes; Thomas-Black, Gilbert; Solanky, Nita; Jansen-West, Karen R; Hanna Al-Shaikh, Rana; Heslegrave, Amanda; Zetterberg, Henrik; Santana, Magda M; Pereira de Almeida, Luis; Vasconcelos-Ferreira, Ana; Januário, Cristina; Infante, Jon; Faber, Jennifer; Klockgether, Thomas; Reetz, Kathrin; Raposo, Mafalda; Ferreira, Ana F; Lima, Manuela; Schöls, Ludger; Synofzik, Matthis; Hübener-Schmid, Jeannette; Puschmann, Andreas; Gorcenco, Sorina; Wszolek, Zbigniew K; Petrucelli, Leonard; Giunti, Paola; - view fewer <#> (2022) Tau and neurofilament light-chain as fluid biomarkers in spinocerebellar ataxia type 3. European Journal of Neurology , 29 (8) pp. 2439-2452. 10.1111/ene.15373 <https://doi.org/10.1111/ene.15373>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10147819/1/Euro%20J%20of%20Neurology%20-%202022%20-%20Garcia%E2%80%90Moreno%20-%20Tau%20and%20neurofilament%20light%E2%80%90chain%20as%20fluid%20biomarkers%20in%20spinocerebellar.pdf