Article
Clinical Neurology
Ioanna Pachi, Christos Koros, Athina M. Simitsi, Dimitra Papadimitriou, Anastasia Bougea, Andreas Prentakis, Nikolaos Papagiannakis, Maria Bozi, Roubina Antonelou, Efthalia Angelopoulou, Ion Beratis, Maria Stamelou, Xenia Geronicola Trapali, Sokratis G. Papageorgiou, Leonidas Stefanis
Summary: This study found that non-manifesting GBA carriers were more likely to present symptoms of apathy compared to healthy controls, even after adjusting for covariates. The prevalence of apathy in LRRK2 carriers was marginally non-significant. GBA carriers were also more likely to develop features of anxiety compared to LRRK2 carriers. Other neuropsychiatric symptoms did not differ between the groups. Longitudinal data with detailed neuropsychiatric evaluation and neuroimaging would be essential for further investigating the pathophysiological basis of these findings.
PARKINSONISM & RELATED DISORDERS
(2021)
Article
Neurosciences
Tanya Simuni, Kalpana Merchant, Michael C. Brumm, Hyunkeun Cho, Chelsea Caspell-Garcia, Christopher S. Coffey, Lana M. Chahine, Roy N. Alcalay, Kelly Nudelman, Tatiana Foroud, Brit Mollenhauer, Andrew Siderowf, Caroline Tanner, Hirotaka Iwaki, Todd Sherer, Kenneth Marek
Summary: This study examined the longitudinal changes in clinical features and biomarkers in LRRK2 non-manifesting carriers (NMCs) versus healthy controls (HCs). The results showed that there were no significant changes in clinical measures or biomarkers over a 2-year period in LRRK2 NMCs, even in those with baseline dopamine transporter (DAT) deficit.
NPJ PARKINSONS DISEASE
(2022)
Article
Clinical Neurology
Eileen E. Moran, Susan B. Bressman, Roberto A. Ortega, Deborah Raymond, William C. Nichols, Christina A. Palmese, Sonya Elango, Matthew Swan, Vicki Shanker, Imali Perera, Cuiling Wang, Molly E. Zimmerman, Rachel Saunders-Pullman
Summary: Mutations and variants in the glucocerebrosidase (GBA) gene are common genetic risk factors for Parkinson's disease (PD), but carriers without PD show poorer performance in executive functioning while no significant differences are observed in other domains. This suggests that most GBA mutation carriers may not present pre-manifest non-motor or motor features associated with PD.
FRONTIERS IN NEUROLOGY
(2021)
Article
Chemistry, Analytical
Eden Shkury, Shani Danziger-Schragenheim, Zoya Katzir, Yael Ezra, Nir Giladi, Anat Mirelman, Inbal Maidan
Summary: This study investigated the neurophysiological changes in Parkinson's disease patients with and without the G2019S-LRRK2 gene mutation. The results showed that patients with the mutation performed better in cognitive tasks and exhibited more efficient early cognitive processes, which may contribute to their better cognitive performance.
Article
Neurosciences
Shi-Shuang Cui, Rao Fu, Juan-Juan Du, Yi-Qi Lin, Pei Huang, Chao Gao, Hai-Yan Zhou, Sheng-Di Chen
Summary: This study found that female PD patients, both carriers and non-carriers of LRRK2 G2385R variants, exhibited a more benign disease course compared to male patients. However, sex differences were less pronounced in PD patients with LRRK2 G2385R variants.
Article
Clinical Neurology
Alicia Garrido, Enrique Santamaria, Joaquin Fernandez-Irigoyen, Marta Soto, Cristina Simonet, Manel Fernandez, Donina Obiang, Eduardo Tolosa, Maria-Jose Marti, Shalini Padmanabhan, Cristina Malagelada, Mario Ezquerra, Ruben Fernandez-Santiago
Summary: This study investigated protein and phospho-protein changes related to the G2019S mutant LRRK2 and identified specific phospho-protein changes associated with disease status. The findings can help distinguish different patient groups.
MOVEMENT DISORDERS
(2022)
Review
Biochemistry & Molecular Biology
Maria Dolores Perez-Carrion, Inmaculada Posadas, Javier Solera, Valentin Cena
Summary: This review summarizes the main pathological mutations in LRRK2 that contribute to Parkinson's disease and discusses the different cellular and therapeutic strategies to correct LRRK2 homeostasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Marta Soto, Manel Fernandez, Paloma Bravo, Sara Lahoz, Alicia Garrido, Antonio Sanchez-Rodriguez, Maria Rivera-Sanchez, Maria Sierra, Paula Melon, Ana Roig-Garcia, Anna Naito, Bradford Casey, Jordi Camps, Eduardo Tolosa, Maria-Jose Marti, Jon Infante, Mario Ezquerra, Ruben Fernandez-Santiago
Summary: The LRRK2 G2019S mutation is associated with Parkinson's disease, but its penetrance is not complete. By longitudinally assessing miRNA expression in serum samples from individuals with the G2019S mutation who have not developed PD symptoms, the researchers identified potential biomarkers for premotor stages of PD. They also found miRNAs that have the potential to be early progression biomarkers for PD.
NPJ PARKINSONS DISEASE
(2023)
Article
Neurosciences
Maria Paulina Castelo Rueda, Alessandra Zanon, Valentina Gilmozzi, Alexandros A. Lavdas, Athina Raftopoulou, Sylvie Delcambre, Fabiola Del Greco, Christine Klein, Anne Gruenewald, Peter P. Pramstaller, Andrew A. Hicks, Irene Pichler
Summary: Homozygous or compound heterozygous variants in PRKN are causal for PD with highly penetrant symptom expression, while heterozygous variants may predispose to PD with reduced penetrance, through altered mitochondrial function. We generated lymphoblasts and hiPSC-derived neurons from non-manifesting heterozygous PRKN variant carriers and tested them for mitochondrial functionality. We identified molecular phenotypes that might be used to monitor heterozygous PRKN variant carriers during the prodromal phase and to test potential neuroprotective therapies.
NPJ PARKINSONS DISEASE
(2023)
Article
Multidisciplinary Sciences
Ranjan K. Singh, Ahmed Soliman, Giambattista Guaitoli, Eliza Stoermer, Felix von Zweydorf, Thomas Dal Maso, Asmaa Oun, Laura Van Rillaer, Sven H. Schmidt, Deep Chatterjee, Joshua A. David, Els Pardon, Thomas U. Schwartz, Stefan Knapp, Eileen J. Kennedy, Jan Steyaert, Friedrich W. Herberg, Arjan Kortholt, Christian Johannes Gloeckner, Wim Versees
Summary: Mutations in the LRRK2 gene are a leading cause of Parkinson's disease, while overactivation of LRRK2 is associated with idiopathic form of the disease. Researchers have identified and characterized nanobodies that can bind to different domains of LRRK2 and inhibit or activate its activity. These nanobodies act through an allosteric inhibitor mechanism and provide potential therapeutic strategies for Parkinson's disease.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Clinical Neurology
Sokratis Charisis, Eva Ntanasi, Maria Stamelou, Georgia Xiromerisiou, Maria Maraki, Aristidis S. Veskoukis, Mary Yannakoulia, Mary H. Kosmidis, Costas A. Anastasiou, Nikolaos Giagkou, Efthimios Dardiotis, Georgios Hadjigeorgiou, Paraskevi Sakka, Demetrios Kouretas, Leonidas Stefanis, Nikolaos Scarmeas
Summary: The study explores the potential role of plasma GSH as a risk/susceptibility biomarker for prodromal PD and finds that higher plasma GSH levels are associated with slower increases in pPD probability, potentially aiding in the identification of individuals likely to be diagnosed with pPD more rapidly.
MOVEMENT DISORDERS
(2022)
Review
Biochemistry & Molecular Biology
Jasmin Galper, Woojin S. Kim, Nicolas Dzamko
Summary: Genetic alterations in the LRRK2 gene are a common risk factor for Parkinson's disease. LRRK2 alterations are associated with changes in lipid pathways, which can lead to cellular pathology.
Article
Clinical Neurology
Eva Schaeffer, Inken Toedt, Susanne Koehler, Annette Rogge, Daniela Berg
Summary: Significant progress has been made in understanding the prodromal phase of Parkinson's disease, leading to the development of disease prediction models. However, diagnostic uncertainty and lack of therapeutic options have raised ethical issues that need further attention. The differentiation between individuals with and without REM sleep behavior disorder (RBD) is crucial in prognostic counseling for prodromal PD.
MOVEMENT DISORDERS
(2021)
Article
Biochemistry & Molecular Biology
Danial Kazemi, Hamed Hajishah, Amir Shayan Chadeganipour
Summary: Oxidative stress is a possible mechanism in Parkinson's disease progression. Total bilirubin is associated with motor signs and asymmetry in early stages of the disease, and shows a significant relationship with motor asymmetry in patients with Hoehn and Yahr stage I.
JOURNAL OF MOLECULAR NEUROSCIENCE
(2022)
Review
Medicine, General & Internal
Xiao-Yan Yao, Li-Na Guan, Qi Chen, Chao Ren
Summary: The pathogenesis of Parkinson's disease involves multiple factors such as heredity, environment, and ageing. Mutations in LRRK2 are recognized as risk factors and play a significant role in the degeneration of dopaminergic neurons in PD. Glial hyperactivation-mediated neuroinflammation is also involved in the development of PD.
POSTGRADUATE MEDICAL JOURNAL
(2023)
Article
Clinical Neurology
Tanya Simuni, Liz Uribe, Hyunkeun Ryan Cho, Chelsea Caspell-Garcia, Christopher S. Coffey, Andrew Siderowf, John Q. Trojanowski, Leslie M. Shaw, John Seibyl, Andrew Singleton, Arthur W. Toga, Doug Galasko, Tatiana Foroud, Duygu Tosun, Kathleen Poston, Daniel Weintraub, Brit Mollenhauer, Caroline M. Tanner, Karl Kieburtz, Lana M. Chahine, Alyssa Reimer, Samantha J. Hutten, Susan Bressman, Kenneth Marek, Vanessa Arnedo, Adrienne Clark, Mark Fraiser, Catherine Kopil, Sohini Chowdhury, Todd Sherer, Nichole Daegele, Christina Salerno, Cynthia Casaceli, Ray Dorsey, Renee Wilson, Sugi Mahes, Karen Crawford, Paola Casalin, Giulia Malferrari, Mali GaniWeisz, Avi Orr-Urtreger, Thomas Montine, Chris Baglieri, Amanda Christini, David Russell, Nabila Dahodwala, Nir Giladi, Stewart Factor, Penelope Hogarth, David Standaert, Robert Hauser, Joseph Jankovic, Marie Saint-Hilaire, Irene Richard, David Shprecher, Hubert Fernandez, Katrina Brockmann, Liana Rosenthal, Paolo Barone, Alberto Espay, Dominic Rowe, Karen Marder, Anthony Santiago, Shu-Ching Hu, Stuart Isaacson, Jean-Christophe Corvol, Javiar Ruiz Martinez, Eduardo Tolosa, Yen Tai, Marios Politis, Debra Smejdir, Linda Rees, Karen Williams, Farah Kausar, Karen Williams, Whitney Richardson, Diana Willeke, Shawnees Peacock, Barbara Sommerfeld, Alison Freed, Katrina Wakeman, Courtney Blair, Stephanie Guthrie, Leigh Harrell, Christine Hunter, Cathi-Ann Thomas, Raymond James, Grace Zimmerman, Victoria Brown, Jennifer Mule, Ella Hilt, Kori Ribb, Susan Ainscough, Misty Wethington, Madelaine Ranola, Helen Mejia Santana, Juliana Moreno, Deborah Raymond, Krista Speketer, Stephanie Carvalo, Ioana Croitoru, Alicia Garrido, Laura Marie Payne, Veena Viswanth, Lawrence Severt, Maurizio Facheris, Holly Soares, Mark A. Mintun, Jesse Cedarbaum, Peggy Taylor, Kevin Biglan, Emily Vandenbroucke, Zulfiqar Haider Sheikh, Baris Bingol, Tanya Fischer, Pablo Sardi, Remi Forrat, Alastair Reith, Jan Egebjerg, Gabrielle Ahlberg Hillert, Barbara Saba, Chris Min, Robert Umek, Joe Mather, Susan De Santi, Anke Post, Frank Boess, Kirsten Taylor, Igor Grachev, Andreja Avbersek, Pierandrea Muglia, Kaplana Merchant, Johannes Tauscher
Article
Clinical Neurology
Anat Mirelman, Inbar Hillel, Lynn Rochester, Silvia Del Din, Bastiaan R. Bloem, Laura Avanzino, Alice Nieuwboer, Inbal Maidan, Talia Herman, Avner Thaler, Tanya Gurevich, Meir Kestenbaum, Avi Orr-Urtreger, Mirek Brys, Jesse M. Cederbaum, Nir Giladi, Jeffrey M. Hausdorff
MOVEMENT DISORDERS
(2020)
Article
Clinical Neurology
Talia Herman, Moria Dagan, Shirley Shema-Shiratzky, Tal Reches, Marina Brozgol, Nir Giladi, Brad Manor, Jeffrey M. Hausdorff
JOURNAL OF NEUROLOGY
(2020)
Article
Clinical Neurology
Nurit Omer, Nir Giladi, Tanya Gurevich, Anat Bar-Shira, Mali Gana-Weisz, Orly Goldstein, Meir Kestenbaum, Jesse M. Cedarbaum, Avi Orr-Urtreger, Anat Mirelman, Avner Thaler
MOVEMENT DISORDERS
(2020)
Article
Multidisciplinary Sciences
Avner Thaler, Shani Shenhar-Tsarfaty, Yanay Shaked, Tanya Gurevich, Nurit Omer, Anat Bar-Shira, Mali Gana-Weisz, Orly Goldstein, Meir Kestenbaum, Jesse M. Cedarbaum, Avi Orr-Urtreger, Nir Giladi, Anat Mirelman
SCIENTIFIC REPORTS
(2020)
Article
Engineering, Biomedical
Nofar Schneider, Moria Dagan, Racheli Katz, Pablo Cornejo Thumm, Marina Brozgol, Nir Giladi, Brad Manor, Anat Mirelman, Jeffery M. Hausdorff
Summary: The study found that tDCS during challenging walking decreased the dual-task cost to walking in older adults. These results support the presence of a state-dependent impact of neuro-modulation.
JOURNAL OF NEUROENGINEERING AND REHABILITATION
(2021)
Article
Clinical Neurology
Anat Mirelman, Mor Ben Or Frank, Michal Melamed, Lena Granovsky, Alice Nieuwboer, Lynn Rochester, Silvia Del Din, Laura Avanzino, Elisa Pelosin, Bastiaan R. Bloem, Ugo Della Croce, Andrea Cereatti, Paolo Bonato, Richard Camicioli, Theresa Ellis, Jamie L. Hamilton, Chris J. Hass, Quincy J. Almeida, Maidan Inbal, Avner Thaler, Julia Shirvan, Jesse M. Cedarbaum, Nir Giladi, Jeffrey M. Hausdorff
Summary: This study utilized wearable sensors to record gait and mobility measures in PD patients and healthy controls, and applied machine-learning algorithms to distinguish between different stages of PD severity. The findings suggest that gait and mobility measures can reflect distinct PD stages with high discriminatory values.
MOVEMENT DISORDERS
(2021)
Article
Clinical Neurology
Brad Manor, Moria Dagan, Talia Herman, Natalia A. Gouskova, Veronique G. Vanderhorst, Nir Giladi, Thomas G. Travison, Alvaro Pascual-Leone, Lewis A. Lipsitz, Jeffrey M. Hausdorff
Summary: This study found that multi-session transcranial direct current stimulation targeting the left dorsolateral prefrontal cortex and primary motor cortex did not significantly improve laboratory-based FOG-provoking test performance, but showed some improvement in patients with mild-to-moderate FOG severity.
MOVEMENT DISORDERS
(2021)
Article
Geriatrics & Gerontology
Tamir Eisenstein, Nir Giladi, Talma Hendler, Ofer Havakuk, Yulia Lerner
Summary: The study found that aerobic activity and cardiorespiratory fitness in older adults are associated with neurocognitive abilities and identified potential neural pathways mediating this relationship. The results support a neuroprotective role of aerobic exercise on the aging brain.
NEUROBIOLOGY OF AGING
(2022)
Article
Clinical Neurology
Inbal Maidan, Noa Zifman, Jeffrey M. Hausdorff, Nir Giladi, Ofri Levy-Lamdan, Anat Mirelman
Summary: The study investigated specific changes in electrical brain activity in response to stimulation of four brain areas in patients with Parkinson's disease (PD) using a combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) assessment. Patients with PD showed lower waveform adherence, lower early phase deflection, lower inter-trial adherence, and lower connectivity between homologous brain areas compared to healthy controls. The findings suggest various alterations in neurophysiological measures in PD patients, indicating different aspects related to the pathophysiology of the disease.
PARKINSONISM & RELATED DISORDERS
(2021)
Article
Clinical Neurology
Nir Giladi, Tanya Gurevich, Ruth Djaldetti, Liat Adar, Ryan Case, Shelly Leibman-Barak, Nissim Sasson, Yoseph Caraco
Summary: ND0612, a continuous subcutaneous levodopa/carbidopa delivery system, was well-tolerated and resulted in reduced OFF time and decreased plasma levodopa fluctuations when used adjunctively in PD patients. Although most patients experienced infusion site nodules, they all resolved without sequelae.
PARKINSONISM & RELATED DISORDERS
(2021)
Article
Clinical Neurology
Mor Yam, Sigal Glatt, Shai Nosatzki, Anat Mirelman, Jeffrey M. Hausdorff, Lilach Goldstein, Nir Giladi, Firas Fahoum, Inbal Maidan
Summary: Juvenile myoclonic epilepsy (JME) is a common epileptic syndrome, and drug resistance is a significant issue. This study found that drug-resistant JME patients have altered brain activity during highly demanding tasks that combine cognitive and motor functions.
FRONTIERS IN NEUROLOGY
(2022)
Article
Chemistry, Analytical
Dan Z. Milikovsky, Yotam Sharabi, Nir Giladi, Anat Mirelman, Ronen Sosnik, Firas Fahoum, Inbal Maidan
Summary: This study aimed to examine the presence of paroxysmal slow-wave events (PSWE) as a biomarker for cortical involvement in Parkinson's disease (PD). The results showed no significant differences in the number of PSWEs between PD patients and controls in all brain regions. However, the correlation between PSWEs and disease duration suggests early signs of cortical involvement in PD.
Article
Clinical Neurology
Shachar Shani, Orly Goldstein, Mali Gana-Weisz, Anat Bar-Shira, Avner Thaler, Tanya Gurevich, Anat Mirelman, Nir Giladi, Roy N. Alcalay, Avi Orr-Urtreger
Summary: Recent studies have found a link between Parkinson's disease (PD) and changes in the innate immune system. This study aimed to determine if genetic variations in innate immune genes are differentially associated with PD in different subgroups, including GBA-PD, LRRK2-PD, and non-carrier PD (NC-PD).
PARKINSONISM & RELATED DISORDERS
(2023)
Article
Chemistry, Analytical
Eden Shkury, Shani Danziger-Schragenheim, Zoya Katzir, Yael Ezra, Nir Giladi, Anat Mirelman, Inbal Maidan
Summary: This study investigated the neurophysiological changes in Parkinson's disease patients with and without the G2019S-LRRK2 gene mutation. The results showed that patients with the mutation performed better in cognitive tasks and exhibited more efficient early cognitive processes, which may contribute to their better cognitive performance.