Unraveling the role of GBA1 genotype in axial signs response to subthalamic deep brain stimulation
GBA1 variants represent the most common genetic risk factor for Parkinson's disease (PD) and are associated with higher risk of developing cognitive decline and axial motor impairment. While cognitive outcomes following subthalamic deep brain stimulation (STN-DBS) have recently received growing attention, axial signs progression remains poorly defined in this population. In this retrospective multicentric study, we analyzed a cohort of 353 PD patients who underwent bilateral STN-DBS surgery (75 GBA+ and 253 GBA-). 5-year follow-up data were available for 233 patients, including 43 mutated subjects. Lower off-medication UPDRS III score and levodopa responsiveness at baseline were identified as independent predictors of axial signs worsening after DBS, while GBA1 genotype was not identified as risk factor. The presence of GBA1 variants did not exert a detrimental effect on axial signs in PD patients up to five years following STN-DBS, supporting its consideration as a valid therapeutic option in this genetic subgroup.
Authors
- Nicoletta Manzo (ORCID: https://orcid.org/0000-0001-7390-4244)
- Valeria Camparini
- Diego Centonze (ORCID: https://orcid.org/0000-0002-8390-8545)
- Barbara Picconi (ORCID: https://orcid.org/0000-0001-6020-1021)
- Ilaria Trezzi (ORCID: https://orcid.org/0000-0002-0177-1021)
- Cristina Limatola (ORCID: https://orcid.org/0000-0001-7504-8197)
- Daniela Di Giuda (ORCID: https://orcid.org/0000-0002-5758-3986)
- Alberto Malovini (ORCID: https://orcid.org/0000-0003-2857-5773)
- Fabio Blandini (ORCID: https://orcid.org/0000-0002-0178-1289)
- Pietro Ghedini (ORCID: https://orcid.org/0000-0002-8590-277X)
- Mariarosa Terreni
- Konstantinos Koutsikos (ORCID: https://orcid.org/0009-0007-9482-4068)
- Marco J. Morelli (ORCID: https://orcid.org/0000-0003-1862-667X)
- Roberto Bergamaschi (ORCID: https://orcid.org/0000-0002-1397-511X)
- Francesca Mameli (ORCID: https://orcid.org/0000-0003-4774-582X)
- Francesco Cavallieri (ORCID: https://orcid.org/0000-0001-5836-1982)
- Daniele Belvisi (ORCID: https://orcid.org/0000-0001-8681-3050)
- Luca Roccatagliata (ORCID: https://orcid.org/0000-0001-8029-3947)
- Sandro Sorbi (ORCID: https://orcid.org/0000-0002-0380-6670)
- Giuseppina Ferrara
- R. Zangaglia
- Anna Losurdo (ORCID: https://orcid.org/0000-0003-3557-8729)
- Luigi Gianolli
- Andrea Arighi (ORCID: https://orcid.org/0000-0003-2865-3970)
- Alessandro De Biase (ORCID: https://orcid.org/0000-0003-2419-1668)
- Valentina D’Onofrio (ORCID: https://orcid.org/0000-0002-5898-0967)
- Barbara Garavaglia
- A. Fiorentino (ORCID: https://orcid.org/0000-0003-2842-4350)
- Elisa Brigonzi (ORCID: https://orcid.org/0000-0002-5017-1890)
- Tiziana De Santis (ORCID: https://orcid.org/0000-0001-7591-7428)
- Stefania Lalli (ORCID: https://orcid.org/0000-0003-1133-0155)
- Andrea Mannini (ORCID: https://orcid.org/0000-0003-0760-052X)
- Viviana Lo Buono (ORCID: https://orcid.org/0000-0001-8027-6098)
- Caterina Pistarini (ORCID: https://orcid.org/0000-0001-8925-0484)
- Caterina Tonon (ORCID: https://orcid.org/0000-0002-0506-499X)
- Francesco Bove (ORCID: https://orcid.org/0000-0002-2959-6659)
- Martina Volonté (ORCID: https://orcid.org/0009-0006-2688-9065)
- J. Sassone
- Federica Vannetti (ORCID: https://orcid.org/0000-0001-9403-7944)
- Ernesto Losavio (ORCID: https://orcid.org/0000-0002-9038-5826)
- Federica Agosta (ORCID: https://orcid.org/0000-0003-3121-4979)
- Antonia Ratti (ORCID: https://orcid.org/0000-0002-4264-6614)
- Carlo Caltagirone (ORCID: https://orcid.org/0000-0002-0189-4515)
- Stefano Puglisi‐Allegra (ORCID: https://orcid.org/0000-0002-9433-2000)
- Antonio Pisani (ORCID: https://orcid.org/0000-0002-8432-594X)
- Roberta Mancuso (ORCID: https://orcid.org/0000-0002-4449-3623)
- Piero Parchi (ORCID: https://orcid.org/0000-0002-9444-9524)
- Massimo Castellani (ORCID: https://orcid.org/0000-0002-9217-3456)
- Giorgio Giaccone (ORCID: https://orcid.org/0000-0002-4803-0802)
- Irene Tramacere (ORCID: https://orcid.org/0000-0001-5550-3412)
- F. Nonino
- Claudio Pacchetti (ORCID: https://orcid.org/0000-0001-8236-9650)
- Alfredo Berardelli (ORCID: https://orcid.org/0000-0003-3598-3142)
- B. Reggiori
- Caterina Galandra (ORCID: https://orcid.org/0000-0002-7048-814X)
- Stefano Bonassi (ORCID: https://orcid.org/0000-0003-3833-6717)
- Laura Avanzino (ORCID: https://orcid.org/0000-0001-6286-1509)
- Vincenzo Silani (ORCID: https://orcid.org/0000-0002-7698-3854)
- P. M. Rossini
- Rosangela Ferese (ORCID: https://orcid.org/0000-0001-8899-0309)
- Vania Broccoli (ORCID: https://orcid.org/0000-0003-4050-0926)
- Eugenio Parati (ORCID: https://orcid.org/0000-0001-5020-6523)
- Giulia Di Lazzaro (ORCID: https://orcid.org/0000-0003-2413-1788)
- R. Pantieri
- Elena Perdixi (ORCID: https://orcid.org/0000-0003-1194-2004)
- Ilaria Cani (ORCID: https://orcid.org/0000-0002-9189-1982)
- Fabrizio Piras (ORCID: https://orcid.org/0000-0003-3566-5494)
- Maria Nolano (ORCID: https://orcid.org/0000-0002-4849-1318)
- Anna Rita Bentivoglio (ORCID: https://orcid.org/0000-0002-9663-095X)
- Edoardo Pelosin
- Valentina Leta (ORCID: https://orcid.org/0000-0002-5794-7540)
- Maria Giulia Bacalini (ORCID: https://orcid.org/0000-0003-1618-2673)
- Elisa Scola (ORCID: https://orcid.org/0000-0001-9056-4122)
- Valentina Fioravanti (ORCID: https://orcid.org/0009-0003-4631-8591)
- Marina Grisoli (ORCID: https://orcid.org/0000-0002-7663-446X)
- Paola Mandich (ORCID: https://orcid.org/0000-0003-3123-3512)
- Francesco Brancati (ORCID: https://orcid.org/0000-0003-3624-2354)
- Carla Piano (ORCID: https://orcid.org/0000-0003-0265-7666)
- Michele Terzaghi (ORCID: https://orcid.org/0000-0001-9692-2218)
- Daniella Genovese
- A. Pichiecchio
- Francesca Valentino (ORCID: https://orcid.org/0000-0002-7641-9938)
- Antonella Peppe (ORCID: https://orcid.org/0000-0003-2676-1695)
- Paolo Polverino (ORCID: https://orcid.org/0000-0003-0798-0171)
- Lidija Antunovic (ORCID: https://orcid.org/0000-0003-1832-1083)
- Pietro Guaraldi (ORCID: https://orcid.org/0000-0003-0597-603X)
- Luisa Sambati (ORCID: https://orcid.org/0000-0002-5939-7933)
- Luca Maderna (ORCID: https://orcid.org/0000-0002-7589-6249)
- R. Campini
- S Galantucci
- Leonardo Caporali (ORCID: https://orcid.org/0000-0002-0666-4380)
- Rita Barresi (ORCID: https://orcid.org/0000-0001-7351-959X)
- Silvia Zabberoni (ORCID: https://orcid.org/0000-0001-8061-0738)
- Antonio Caronni (ORCID: https://orcid.org/0000-0003-3051-1031)
- Alessandro Izzo (ORCID: https://orcid.org/0000-0003-3145-7313)
- Francesca De Giorgi (ORCID: https://orcid.org/0000-0003-4850-3582)
- Roberto Cilia (ORCID: https://orcid.org/0000-0002-1990-1939)
- Roberta Marchese (ORCID: https://orcid.org/0000-0003-2321-088X)
- Nicola Ticozzi (ORCID: https://orcid.org/0000-0001-5963-7426)
- G. Bonanno (ORCID: https://orcid.org/0000-0002-4792-3983)
- Andrea Ciammola (ORCID: https://orcid.org/0000-0001-8684-165X)
- Mario Meloni (ORCID: https://orcid.org/0000-0002-6319-3458)
- Roberta Calabrese (ORCID: https://orcid.org/0000-0002-4363-3372)
- Ermanno Federici (ORCID: https://orcid.org/0000-0003-4983-1967)
- Riccardo Bellazzi (ORCID: https://orcid.org/0000-0002-6974-9808)
- Andrea Gaudio (ORCID: https://orcid.org/0000-0002-3377-3953)
- Giovanna Lopane (ORCID: https://orcid.org/0000-0002-3383-0516)
- Angelo Antonini (ORCID: https://orcid.org/0000-0003-1040-2807)
- Giuliano Zebellin
- Leonardo Lopiano (ORCID: https://orcid.org/0000-0001-9098-387X)
- Marta Picascia (ORCID: https://orcid.org/0000-0001-6774-0159)
- Denise Martineli Rossi (ORCID: https://orcid.org/0000-0003-0037-3387)
- Antoniangela Cocco (ORCID: https://orcid.org/0000-0001-9144-1415)
- Giuseppe Di Lorenzo (ORCID: https://orcid.org/0000-0001-7414-1568)
- M. Filippi
- Amelia Brigandì (ORCID: https://orcid.org/0000-0001-9424-6033)
- Edoardo Monfrini (ORCID: https://orcid.org/0000-0003-4720-9234)
- Maria Francesca De Pandis (ORCID: https://orcid.org/0000-0003-1303-4106)
- Elisabetta Capello (ORCID: https://orcid.org/0000-0003-1356-0966)
- Francesca Di Biasio (ORCID: https://orcid.org/0000-0003-3955-8485)
- Filippo Cogiamanian (ORCID: https://orcid.org/0000-0001-7810-5281)
- Silvia Cerri (ORCID: https://orcid.org/0000-0002-6466-5381)
- Lucia Trevisan (ORCID: https://orcid.org/0000-0002-8608-4342)
- Francesca Lea Saibene (ORCID: https://orcid.org/0000-0002-7549-7838)
- Fabio Moda (ORCID: https://orcid.org/0000-0002-2820-9880)
- Roberto Gatti (ORCID: https://orcid.org/0000-0002-4669-1287)
- Stefano Amadio
- A. Albanese
- Roberta Zangaglia (ORCID: https://orcid.org/0000-0002-0962-1845)
- Giorgio Arcara (ORCID: https://orcid.org/0000-0001-6270-6883)
- Raffaella Minardi (ORCID: https://orcid.org/0000-0002-8190-8517)
- Roberto Eleopra (ORCID: https://orcid.org/0000-0002-6035-9715)
- Antonietta Arcella (ORCID: https://orcid.org/0000-0002-0708-8282)
- Sylvie Piacentini (ORCID: https://orcid.org/0000-0003-2640-3281)
- Clelia Pellicano (ORCID: https://orcid.org/0000-0002-3272-1094)
- Alessio Di Fonzo (ORCID: https://orcid.org/0000-0001-6478-026X)
- C. Morasso
- Francesco E. Pontieri (ORCID: https://orcid.org/0000-0002-8693-8432)
- Federico Massa (ORCID: https://orcid.org/0000-0001-5667-204X)
- Federico Verde (ORCID: https://orcid.org/0000-0002-3977-6995)
- Roberto De Icco (ORCID: https://orcid.org/0000-0001-9415-4948)
- Paola Origone
- Giovanna Lagravinese (ORCID: https://orcid.org/0000-0002-6570-3626)
- Cristina Agliardi (ORCID: https://orcid.org/0000-0003-2022-3386)
- Giovanna Calandra–Buonaura (ORCID: https://orcid.org/0000-0002-9447-3532)
- Gabriele Imbalzano (ORCID: https://orcid.org/0000-0002-4842-529X)
- Luigi Romito (ORCID: https://orcid.org/0000-0002-6772-1035)
- Enza Maria Valente (ORCID: https://orcid.org/0000-0002-0600-6820)
- Francesco Colucci (ORCID: https://orcid.org/0000-0001-5193-6376)
- Paola Cudia
- Nicola Modugno (ORCID: https://orcid.org/0000-0001-5243-1775)
- Silvia Marino (ORCID: https://orcid.org/0000-0002-1088-6808)
- Alberto Imarisio (ORCID: https://orcid.org/0000-0002-1206-4170)
- Andrea Guerra (ORCID: https://orcid.org/0000-0001-6601-4964)
- Francesca Baglio (ORCID: https://orcid.org/0000-0002-6145-5274)
- Valério Carelli (ORCID: https://orcid.org/0000-0003-4923-6404)
- Eliana Lauranzano (ORCID: https://orcid.org/0000-0002-9297-3242)
- Flavio Nobili (ORCID: https://orcid.org/0000-0001-9811-0897)
- Barbara Poletti (ORCID: https://orcid.org/0000-0003-4398-2051)
- Cristina Campi (ORCID: https://orcid.org/0000-0003-2105-8554)
- Serena Silvestro (ORCID: https://orcid.org/0000-0003-3846-0785)
- Nico Golfrè Andreasi (ORCID: https://orcid.org/0000-0003-3555-5367)
- Ilaria Palmieri (ORCID: https://orcid.org/0000-0002-0304-7299)
- V. Tibollo
- Giulia Giannini (ORCID: https://orcid.org/0000-0002-0499-3236)
- Maria Grazia Vita
- Danilo Genovese (ORCID: https://orcid.org/0000-0002-7603-5758)
- Federica Provini (ORCID: https://orcid.org/0000-0001-9063-2658)
- Maria Chiara Malaguti (ORCID: https://orcid.org/0000-0002-4807-4063)
- M. Matteoli
- Emanuele Frattini (ORCID: https://orcid.org/0000-0002-5375-2404)
- Maria Rita Lo Monaco (ORCID: https://orcid.org/0000-0002-1457-7981)
- Laura Vacca (ORCID: https://orcid.org/0000-0002-6634-4119)
- Alberto Costa (ORCID: https://orcid.org/0000-0002-4784-5524)
- Giacomo Savini (ORCID: https://orcid.org/0000-0003-0075-3582)
- Antonio Emanuele Elia (ORCID: https://orcid.org/0000-0002-5917-7578)
- Giulia Maria Sancesario (ORCID: https://orcid.org/0000-0001-8365-164X)
- Amelia Cimmino (ORCID: https://orcid.org/0000-0002-0004-9299)
- Luca Boni (ORCID: https://orcid.org/0000-0003-2217-4047)
- Elvezia Maria Paraboschi (ORCID: https://orcid.org/0000-0002-7935-798X)
- Giulio Ferrazzi (ORCID: https://orcid.org/0000-0001-7449-4718)
- Carlo Alberto Artusi (ORCID: https://orcid.org/0000-0001-8579-3772)
- Rosalinda Cardamone
- Francesco Danilo Tiziano (ORCID: https://orcid.org/0000-0002-5545-6158)
- Davide Pozzi (ORCID: https://orcid.org/0000-0001-6436-0556)
- Fabrizio Stocchi (ORCID: https://orcid.org/0000-0002-5763-0033)
- Giuseppe Battaglia (ORCID: https://orcid.org/0000-0001-7571-3417)
- Letterio S. Politi (ORCID: https://orcid.org/0000-0002-6190-6688)
- Fabio Maria Triulzi (ORCID: https://orcid.org/0000-0002-5428-7217)
- Silvia Daniela Morbelli (ORCID: https://orcid.org/0000-0002-7833-6095)
- Michele Gennuso (ORCID: https://orcid.org/0009-0006-9180-3555)
- Giuseppe Cosentino (ORCID: https://orcid.org/0000-0001-8691-3430)
- Elisabetta Sarasso (ORCID: https://orcid.org/0000-0002-5300-2849)
- G Maggioni (ORCID: https://orcid.org/0000-0002-9246-7008)
- Stefano Gambardella (ORCID: https://orcid.org/0000-0002-3727-4502)
- Claudia Ledda (ORCID: https://orcid.org/0000-0003-0839-932X)
- Luca Baldelli (ORCID: https://orcid.org/0000-0003-3666-1735)
- Rossana Mineri (ORCID: https://orcid.org/0000-0002-6636-8954)
- Alessandro Gialluisi (ORCID: https://orcid.org/0000-0002-7388-4463)
- Federica Giardina (ORCID: https://orcid.org/0000-0002-3710-0940)
- Alberto Albanese (ORCID: https://orcid.org/0000-0002-5864-0006)
- Paolo Calabresi (ORCID: https://orcid.org/0000-0003-0326-5509)
- Felice Giangaspero (ORCID: https://orcid.org/0000-0001-5382-2380)
- Grazia Devigili (ORCID: https://orcid.org/0000-0001-9688-4231)
- Fabiana Colucci (ORCID: https://orcid.org/0000-0003-1945-8153)
- Pietro Cortelli (ORCID: https://orcid.org/0000-0002-3633-8818)
- Chiara Sorbera (ORCID: https://orcid.org/0000-0002-5872-3119)
- Fabio Guerini
- Micol Avenali (ORCID: https://orcid.org/0000-0002-7880-9921)
- Martina Petracca (ORCID: https://orcid.org/0000-0001-8033-3785)
- Marco Liccari
- Giada Cuconato
- Pierfrancesco Mitrotti (ORCID: https://orcid.org/0000-0003-3574-1290)
- Christian Lunetta (ORCID: https://orcid.org/0000-0002-4788-1875)
- A. Cocco (ORCID: https://orcid.org/0009-0005-9599-9949)
- Giulia Franco (ORCID: https://orcid.org/0000-0003-0580-3550)
- Mariachiara Buonocore (ORCID: https://orcid.org/0000-0002-9600-6284)
- Franco Valzania
- Andrea De Biase
- C. Tassorelli
- F. M. Cossa
- Patrizia Pantano
- Giovanna Calandra-Buonaura
- L Pavone
- Francesca Sommaruga
- Niccolò Casasoli
- F. Pellizzari
- M. Cribiù
- C. Losa
Institutions
- Università Cattolica del Sacro Cuore (IT)
- University of Padua (IT)
- Università Campus Bio-Medico (IT)
- University of Pavia (IT)
- Agostino Gemelli University Polyclinic (IT)
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- Istituto Neurologico Mediterraneo (IT)
- Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT)
- Ospedale Santa Chiara (IT)
- Azienda Sanitaria Unità Locale di Reggio Emilia (IT)
- Istituti Clinici Scientifici Maugeri (IT)
- Ospedale di Cattinara (IT)
- Don Carlo Gnocchi Foundation (IT)
- Istituto delle Scienze Neurologiche di Bologna (IT)
- IRCCS San Camillo Hospital (IT)
- IRCCS Ospedale San Raffaele (IT)
- IRCCS Istituto Auxologico Italiano (IT)
- Ospedale Policlinico San Martino (IT)
- Fondazione Santa Lucia (IT)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- Ospedale generale di zona San Camillo Treviso (IT)
- Centro Neurolesi Bonino Pulejo (IT)
- IRCCS Humanitas Research Hospital (IT)
- Fondazione IRCCS Istituto Neurologico Carlo Besta (IT)
- Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele (IT)
- University of Turin (IT)
- University of Genoa (IT)
- University of Bologna (IT)
Publication Details
- Journal
- npj Parkinson s Disease
- Published
- 2025-10-17
- DOI
- https://doi.org/10.1038/s41531-025-01140-7
- Primary Topic
- Neurological disorders and treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00