Review
Psychology, Multidisciplinary
Joshua A. Wilt, Amanda R. Merner, Jaclyn Zeigler, Michelle Montpetite, Cynthia S. Kubu
Summary: Deep Brain Stimulation (DBS) is a safe and effective treatment for Parkinson's Disease (PD) in improving motor symptoms, but concerns about its effects on patients' personality remain. Research shows that while there is little evidence of changes in dispositional traits following DBS, there is some positive progress in characteristic adaptations. Further research is needed in exploring the impact on narrative identity after DBS treatment for PD.
FRONTIERS IN PSYCHOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Tohru Kitada, Mustafa T. Ardah, M. Emdadul Haque
Summary: Parkin, discovered 25 years ago as the gene responsible for hereditary Parkinson's disease, remains a subject of intense research interest. Despite extensive efforts, the function and mechanism of the Parkin protein in neuronal cell death and pathogenesis remain unknown. This review highlights the chronological research on the parkin gene and discusses unresolved issues, new trends in research, and the relationship between parkin and tumorigenesis from the perspective of Parkin's redox molecule.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Neurosciences
T. Warnecke, K-H Schaefer, I Claus, K. Del Tredici, W. H. Jost
Summary: Growing evidence suggests that dysfunction of the gastrointestinal tract (GIT) plays a significant role in Parkinson's disease (PD). Most PD patients experience symptoms such as difficulty swallowing, excessive saliva production, bloating, nausea, vomiting, delayed gastric emptying, and constipation. The accumulation of Lewy pathology in the GIT and central nervous system is thought to contribute to these symptoms. Complications, including malnutrition, dehydration, inadequate response to medications, pneumonia, intestinal obstruction, and megacolon, often require hospitalization. Diagnostic tools and novel treatment approaches are being developed, although more high-level evidence trials are needed. Additionally, the role of the GIT microbiome in PD is being increasingly recognized.
NPJ PARKINSONS DISEASE
(2022)
Article
Clinical Neurology
Kurt A. Jellinger
Summary: PDD and DLB are two major neurocognitive disorders in the spectrum of Lewy body diseases with overlapping clinical and neuropathological features. DLB has higher Braak LB scores and neuritic Braak stages, as well as more severe neuropathological features like Thal A beta phases and neuritic Braak stages. Worse prognosis in DLB is linked to increased Braak neuritic stages and more severe cerebral amyloid angiopathy.
PARKINSONISM & RELATED DISORDERS
(2022)
Review
Medicine, General & Internal
Marwan Hariz, Patric Blomstedtl
Summary: Parkinson's disease is a progressive neurodegenerative illness with motor and nonmotor symptoms. Deep brain stimulation is an effective symptomatic treatment that can be tailored to individual patients. DBS has significant effects on tremors, rigidity, and dyskinesias, but less responsive for axial symptoms. Specialized multidisciplinary teams are required for DBS in PD.
JOURNAL OF INTERNAL MEDICINE
(2022)
Article
Clinical Neurology
Karri Kaivola, Zalak Shah, Ruth Chia, Sonja W. Scholz
Summary: The GBA gene is associated with risk for dementia with Lewy bodies (DLB) in patients without the APOE ε4 allele, while the APOE ε4 allele is associated with DLB co-pathology with Alzheimer's disease. APOE ε4 is not an independent driver of alpha-synuclein pathology in pure DLB, but GBA plays a significant role in the pure DLB subgroup.
Article
Clinical Neurology
Martin M. Reich, Joey Hsu, Michael Ferguson, Frederic L. W. V. J. Schaper, Juho Joutsa, Jonas Roothans, Robert C. Nickl, Anneke Frankemolle-Gilbert, Jay Alberts, Jens Volkmann, Michael D. Fox
Summary: The study demonstrates that the decline in cognitive function caused by deep brain stimulation (DBS) is related to the connectivity between the stimulation site and a specific brain network associated with memory impairment. Transforming this network into a heat map can help identify DBS patients at risk of delayed-onset side-effects and guide reprogramming efforts.
Review
Clinical Neurology
Zina Hijazi, Nawaf Yassi, John T. O'Brien, Rosie Watson
Summary: This review examines cerebrovascular lesions in Lewy body dementia (LBD), finding that white matter changes and cerebral microbleeds are common pathological features. Compared to Parkinson's disease without dementia and age-matched controls, LBD patients have increased severity of white matter changes, which is not supported by neuropathological examination. The prevalence of cerebral microbleeds in LBD varies greatly, but is similar to Alzheimer's disease. Larger studies are needed to assess the impact of cerebrovascular lesions on clinical symptoms, disease progression, and outcomes.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Clinical Neurology
Abteen Mostofi, Francesca Morgante, Mark J. Edwards, Peter Brown, Erlick A. C. Pereira
Summary: Pain in Parkinson's disease is often untreated due to lack of understanding of its mechanisms. Deep brain stimulation of the subthalamic nucleus has shown potential in treating pain, but the exact type of pain it benefits and how it interferes with pain processing remain unclear.
Review
Clinical Neurology
Hengameh Zahed, Jose Rafael Pantoja Zuzuarregui, Ro'ee Gilron, Timothy Denison, Philip A. Starr, Simon Little
Summary: Sleep disturbances are common nonmotor complications of Parkinson's disease, potentially contributing to disease progression. Limited options currently exist to modulate sleep disturbances, prompting the need for further research into neurophysiological changes affecting sleep in PD.
MOVEMENT DISORDERS
(2021)
Review
Cell Biology
Jia-Yi Li, Wen Li
Summary: The review focused on fetal dopaminergic neuron transplantation therapies for Parkinson's disease, highlighting the clinical outcomes and neuroanatomy of grafted cases, as well as postmortem studies including cell survival, reinnervation, and pathology development. The discussion aimed at understanding the link between function and structure of the grafts to identify factors contributing to a functional graft for future transplantation trials.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Clinical Neurology
Lais M. Oliveira, Marta Ruiz-Lopez, Alexandre Boutet, Gavin J. B. Elias, Suneil K. Kalia, Mojgan Hodaie, Andres M. Lozano, Renato P. Munhoz, Alfonso Fasano
Summary: The study found that using the advanced functions of the patient programmer delays programming optimization and is associated with a higher number of side effects. Therefore, there is a need for other faster and safer stimulation programming methods.
Article
Clinical Neurology
Kyoungwon Baik, Hye Ryun Kim, Mincheol Park, Younggun Lee, Han Kyu Na, Young H. H. Sohn, Joon-Kyung Seong, Phil Hyu Lee
Summary: This study investigated the effect of amyloid accumulation on cognitive dysfunction in patients with Parkinson's disease and dementia with Lewy bodies. The results showed that while the burden of amyloid was higher in the dementia with Lewy bodies group, amyloid accumulation was negatively associated with memory and language functions only in the Parkinson's disease group.
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Gian D. Pal, Daniel M. Corcos, Leo Verhagen Metman, Zvi Israel, Hagai Bergman, David Arkadir
Summary: Genetic subtyping of patients with Parkinson's disease may help predict the cognitive and motor outcomes of subthalamic deep brain stimulation. However, there are still controversies and gaps in understanding the effects of STN-DBS on PD patients with pathogenic variants in the GBA1 gene. Further research is needed to determine the clinical significance, risk-to-benefit ratio, and strategies to minimize the negative effects of STN-DBS. Genetic testing for GBA1 may be considered in PD patients considering DBS to properly assess the potential risks and benefits.
MOVEMENT DISORDERS
(2023)
Article
Neurosciences
Nikhil Panicker, Tae-In Kam, Hu Wang, Stewart Neifert, Shih-Ching Chou, Manoj Kumar, Saurav Brahmachari, Aanishaa Jhaldiyal, Jared T. Hinkle, Fatih Akkentli, Xiaobo Mao, Enquan Xu, Senthilkumar S. Karuppagounder, Eric T. Hsu, Sung-Ung Kang, Olga Pletnikova, Juan Troncoso, Valina L. Dawson, Ted M. Dawson
Summary: Parkinson's disease is caused by alpha-synuclein accumulation and death of dopamine neurons in the substantia nigra pars compacta, with NLRP3 inflammasome hyperactivation playing a role in the disease. Loss of parkin activity leads to spontaneous assembly of NLRP3 inflammasome in dopamine neurons, which is further exacerbated by mitochondrial-derived reactive oxygen species. Inhibition of neuronal NLRP3 inflammasome assembly can prevent degeneration of dopamine neurons in PD models.
Article
Clinical Neurology
Emil K. Gustavsson, Jordan Follett, Matthew J. Farrer, Jan O. Aasly
Article
Neurosciences
Jordan Follett, Jesse D. Fox, Emil K. Gustavsson, Chelsie Kadgien, Lise N. Munsie, Li Ping Cao, Igor Tatarnikov, Austen J. Milnerwood, Matthew J. Farrer
NEUROSCIENCE LETTERS
(2019)
Article
Clinical Neurology
Zhongbo Chen, Reza Maroofian, A. Nazli Basak, Leena Shingavi, Mert Karakaya, Stephanie Efthymiou, Emil K. Gustavsson, Leyla Meier, Kiran Polavarapu, Seena Vengalil, Veeramani Preethish-Kumar, Bevinahalli N. Nandeesh, Nalan Gokce Gunes, Onur Akan, Fatma Candan, Bertold Schrank, Stephan Zuchner, David Murphy, Mahima Kapoor, Mina Ryten, Brunhilde Wirth, Mary M. Reilly, Atchayaram Nalini, Henry Houlden, Payam Sarraf
Summary: Pathogenic variants in PLEKHG5 have been reported in patients with autosomal recessive intermediate Charcot-Marie-Tooth disease and spinal muscular atrophy. The study identified novel biallelic variants in PLEKHG5 in 13 individuals from nine families, showing variable disease severity and age of onset. The findings suggest PLEKHG5-associated neuropathies as an important differential diagnosis in non-5q spinal muscular atrophy cases, expanding the understanding of the disease spectrum.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Genetics & Heredity
Ruth Chia, Marya S. Sabir, Sara Bandres-Ciga, Sara Saez-Atienzar, Regina H. Reynolds, Emil Gustavsson, Ronald L. Walton, Sarah Ahmed, Coralie Viollet, Jinhui Ding, Mary B. Makarious, Monica Diez-Fairen, Makayla K. Portley, Zalak Shah, Yevgeniya Abramzon, Dena G. Hernandez, Cornelis Blauwendraat, David J. Stone, John Eicher, Laura Parkkinen, Olaf Ansorge, Lorraine Clark, Lawrence S. Honig, Karen Marder, Afina Lemstra, Peter St George-Hyslop, Elisabet Londos, Kevin Morgan, Tammaryn Lashley, Thomas T. Warner, Zane Jaunmuktane, Douglas Galasko, Isabel Santana, Pentti J. Tienari, Liisa Myllykangas, Minna Oinas, Nigel J. Cairns, John C. Morris, Glenda M. Halliday, Vivianna M. Van Deerlin, John Q. Trojanowski, Maurizio Grassano, Andrea Calvo, Gabriele Mora, Antonio Canosa, Gianluca Floris, Ryan C. Bohannan, Francesca Brett, Ziv Gan-Or, Joshua T. Geiger, Anni Moore, Patrick May, Rejko Kruger, David S. Goldstein, Grisel Lopez, Nahid Tayebi, Ellen Sidransky, Lucy Norcliffe-Kaufmann, Jose-Alberto Palma, Horacio Kaufmann, Vikram G. Shakkottai, Matthew Perkins, Kathy L. Newell, Thomas Gasser, Claudia Schulte, Francesco Landi, Erika Salvi, Daniele Cusi, Eliezer Masliah, Ronald C. Kim, Chad A. Caraway, Edwin S. Monuki, Maura Brunetti, Ted M. Dawson, Liana S. Rosenthal, Marilyn S. Albert, Olga Pletnikova, Juan C. Troncoso, Margaret E. Flanagan, Qinwen Mao, Eileen H. Bigio, Eloy Rodriguez-Rodriguez, Jon Infante, Carmen Lage, Isabel Gonzalez-Aramburu, Pascual Sanchez-Juan, Bernardino Ghetti, Julia Keith, Sandra E. Black, Mario Masellis, Ekaterina Rogaeva, Charles Duyckaerts, Alexis Brice, Suzanne Lesage, Georgia Xiromerisiou, Matthew J. Barrett, Bension S. Tilley, Steve Gentleman, Giancarlo Logroscino, Geidy E. Serrano, Thomas G. Beach, Ian G. McKeith, Alan J. Thomas, Johannes Attems, Christopher M. Morris, Laura Palmer, Seth Love, Claire Troakes, Safa Al-Sarraj, Angela K. Hodges, Dag Aarsland, Gregory Klein, Scott M. Kaiser, Randy Woltjer, Pau Pastor, Lynn M. Bekris, James B. Leverenz, Lilah M. Besser, Amanda Kuzma, Alan E. Renton, Alison Goate, David A. Bennett, Clemens R. Scherzer, Huw R. Morris, Raffaele Ferrari, Diego Albani, Stuart Pickering-Brown, Kelley Faber, Walter A. Kukull, Estrella Morenas-Rodriguez, Alberto Lleo, Juan Fortea, Daniel Alcolea, Jordi Clarimon, Mike A. Nalls, Luigi Ferrucci, Susan M. Resnick, Toshiko Tanaka, Tatiana M. Foroud, Neill R. Graff-Radford, Zbigniew K. Wszolek, Tanis Ferman, Bradley F. Boeve, John A. Hardy, Eric J. Topol, Ali Torkamani, Andrew B. Singleton, Mina Ryten, Dennis W. Dickson, Adriano Chio, Owen A. Ross, J. Raphael Gibbs, Clifton L. Dalgard, Bryan J. Traynor, Sonja W. Scholz
Summary: By conducting whole-genome sequencing and genetic analysis, researchers have identified common genetic risk factors and pathways shared between Lewy body dementia, Alzheimer's disease, and Parkinson's disease. This provides a deeper understanding of the complex genetic architecture of these age-related neurodegenerative conditions.
Article
Clinical Neurology
Dongbing Lai, Babak Alipanahi, Pierre Fontanillas, Tae-Hwi Schwantes-An, Jan Aasly, Roy N. Alcalay, Gary W. Beecham, Daniela Berg, Susan Bressman, Alexis Brice, Kathrin Brockman, Lorraine Clark, Mark Cookson, Sayantan Das, Vivianna Van Deerlin, Jordan Follett, Matthew J. Farrer, Joanne Trinh, Thomas Gasser, Stefano Goldwurm, Emil Gustavsson, Christine Klein, Anthony E. Lang, J. William Langston, Jeanne Latourelle, Timothy Lynch, Karen Marder, Connie Marras, Eden R. Martin, Cory Y. McLean, Helen Mejia-Santana, Eric Molho, Richard H. Myers, Karen Nuytemans, Laurie Ozelius, Haydeh Payami, Deborah Raymond, Ekaterina Rogaeva, Michael P. Rogers, Owen A. Ross, Ali Samii, Rachel Saunders-Pullman, Birgitt Schule, Claudia Schulte, William K. Scott, Caroline Tanner, Eduardo Tolosa, James E. Tomkins, Dolores Vilas, John Q. Trojanowski, Ryan Uitti, Jeffery M. Vance, Naomi P. Visanji, Zbigniew K. Wszolek, Cyrus P. Zabetian, Anat Mirelman, Nir Giladi, Avi Orr Urtreger, Paul Cannon, Brian Fiske, Tatiana Foroud
Summary: This study identified a variant in the intronic region of CORO1C that may modify the penetrance of LRRK2 mutations, and common Parkinson's disease associated variants collectively increase the penetrance of LRRK2 mutations.
ANNALS OF NEUROLOGY
(2021)
Article
Multidisciplinary Sciences
Zhongbo Chen, David Zhang, Regina H. Reynolds, Emil K. Gustavsson, Sonia Garcia-Ruiz, Karishma D'Sa, Aine Fairbrother-Browne, Jana Vandrovcova, John Hardy, Henry Houlden, Sarah A. Gagliano Taliun, Juan Botia, Mina Ryten
Summary: Knowledge of genomic features specific to the human lineage may provide insights into brain-related diseases, with certain regions playing a potential role in both brain development and neurological disease.
NATURE COMMUNICATIONS
(2021)
Letter
Clinical Neurology
Nina Asheim Birkeland, Viel Nyborg Carlsen, Sasha Gulati, Emil K. Gustavsson, Jan O. Aasly
Summary: A patient with Parkinson's disease initially rejected for DBS due to extensive brain calcifications underwent successful surgery after seeking a second opinion. Genetic analysis revealed a mutation in the SLC20A2 gene, known to cause brain calcifications, but no known PD-causing mutation.
PARKINSONISM & RELATED DISORDERS
(2022)
Article
Clinical Neurology
Malan Johansen, Sofus Joensen, Marjun Restorff, Tormodur Stora, Darren Christy, Emil K. Gustavsson, Jiang Bian, Yi Guo, Matthew J. Farrer, Maria Skaalum Petersen
Summary: This study revealed the association of APOE and immunogenomic variability with AD and dementia risk in the Faroe Islands. The PRS+APOE based on SNP analysis showed excellent sensitivity and specificity for the diagnosis of AD. High PRSs were also associated with an earlier onset of late-onset AD.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Multidisciplinary Sciences
Anna-Leigh Brown, Oscar G. Wilkins, Matthew J. Keuss, Sarah E. Hill, Matteo Zanovello, Weaverly Colleen Lee, Alexander Bampton, Flora C. Y. Lee, Laura Masino, Yue A. Qi, Sam Bryce-Smith, Ariana Gatt, Martina Hallegger, Delphine Fagegaltier, Hemali Phatnani, Jia Newcombe, Emil K. Gustavsson, Sahba Seddighi, Joel F. Reyes, Steven L. Coon, Daniel Ramos, Giampietro Schiavo, Elizabeth M. C. Fisher, Towfique Raj, Maria Secrier, Tammaryn Lashley, Jernej Ule, Emanuele Buratti, Jack Humphrey, Michael E. Ward, Pietro Fratta
Summary: Risk variants in the synaptic gene UNC13A are associated with increased risk of ALS and FTD. These variants lead to the inclusion of a cryptic exon in UNC13A when TDP-43 is depleted, resulting in the loss of UNC13A protein. Two common UNC13A polymorphisms strongly associated with ALS and FTD risk overlap with TDP-43 binding sites.
Article
Biochemical Research Methods
Emil K. Gustavsson, David Zhang, Regina H. Reynolds, Sonia Garcia-Ruiz, Mina Ryten
Summary: ggtranscript is a fast and flexible tool for visualizing and comparing transcripts, inheriting the functionality and familiarity of ggplot2 for easy use.
Article
Clinical Neurology
Zhongbo Chen, Arianna Tucci, Valentina Cipriani, Emil K. Gustavsson, Kristina Ibanez, Regina H. Reynolds, David Zhang, Letizia Vestito, Alejandro Cisterna Garcia, Siddharth Sethi, Jonathan W. Brenton, Sonia Garcia-Ruiz, Aine Fairbrother-Browne, Ana-Luisa Gil-Martinez, Nick Wood, John A. Hardy, Damian Smedley, Henry Houlden, Juan Botia, Mina Ryten
Summary: Using a systems biology approach, Chen et al. found that genes associated with adult- and child-onset ataxia share common characteristics, including a high density of short tandem repeats. Removing the age-of-onset partition and screening for repeat expansions could improve the diagnosis of hereditary ataxia.
Article
Biochemistry & Molecular Biology
Sonia Garcia-Ruiz, Emil K. Gustavsson, David Zhang, Regina H. Reynolds, Zhongbo Chen, Aine Fairbrother-Browne, Ana Luisa Gil-Martinez, Juan A. Botia, Leonardo Collado-Torres, Mina Ryten
Summary: Dysregulation of RNA splicing is implicated in rare and complex diseases. We have developed IntroVerse, a comprehensive resource for exploring intron usage by providing a catalogue of annotated introns and novel junctions. This dataset, generated from extensive RNA sequencing analysis, offers insights into novel transcripts and assessment of splicing noise in introns.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Lynne Krohn, Karl Heilbron, Cornelis Blauwendraat, Regina H. Reynolds, Eric Yu, Konstantin Senkevich, Uladzislau Rudakou, Mehrdad A. Estiar, Emil K. Gustavsson, Kajsa Brolin, Jennifer A. Ruskey, Kathryn Freeman, Farnaz Asayesh, Ruth Chia, Isabelle Arnulf, Michele T. M. Hu, Jacques Y. Montplaisir, Jean-Francois Gagnon, Alex Desautels, Yves Dauvilliers, Gian Luigi Gigli, Mariarosaria Valente, Francesco Janes, Andrea Bernardini, Birgit Hogl, Ambra Stefani, Abubaker Ibrahim, Karel Sonka, David Kemlink, Wolfgang Oertel, Annette Janzen, Giuseppe Plazzi, Francesco Biscarini, Elena Antelmi, Michela Figorilli, Monica Puligheddu, Brit Mollenhauer, Claudia Trenkwalder, Friederike Sixel-Doring, Valerie Cochen De Cock, Christelle Charley Monaca, Anna Heidbreder, Luigi Ferini-Strambi, Femke Dijkstra, Mineke Viaene, Beatriz Abril, Bradley F. Boeve, Sonja W. Scholz, Mina Ryte, Sara Bandres-Ciga, Alastair Noyce, Paul Cannon, Lasse Pihlstrom, Mike A. Nalls, Andrew B. Singleton, Guy A. Rouleau, Ronald B. Postuma, Ziv Gan-Or
Summary: The study identifies five RBD risk loci and highlights the differential expression of SNCA-AS1 and SCARB2 genes in different brain regions. These findings provide further insights into the genetics of RBD and its potential for early intervention.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
Stefano Cataldi, Jordan Follett, Jesse D. Fox, Igor Tatarnikov, Chelsie Kadgien, Emil K. Gustavsson, Jaskaran Khinda, Austen J. Milnerwood, Matthew J. Farrer
NPJ PARKINSONS DISEASE
(2018)