Article
Cell Biology
Ting Shen, Jia-Li Pu, Ya-Si Jiang, Yu-Mei Yue, Ting-Ting He, Bo-Yi Qu, Shuai Zhao, Ya-Ping Yan, Hsin-Yi Lai, Bao-Rong Zhang
Summary: This study investigates the effects of multiple single nucleotide polymorphisms on brain imaging phenotype in Parkinson's disease. The findings suggest that the cognitive-weighted polygenic risk score is correlated with neural activity and connectivity in specific brain regions, as well as gray matter alterations. Additionally, single nucleotide polymorphisms in certain genes are associated with white matter microstructural changes and visual cognitive dysfunction.
NEURAL REGENERATION RESEARCH
(2023)
Article
Clinical Neurology
Marina Picillo, Raffaele Palladino, Roberto Erro, Rossella Alfano, Carlo Colosimo, Roberto Marconi, Angelo Antonini, Paolo Barone
Summary: In women, prodromal constipation is associated with attention/memory complaints and apathy symptoms. In older patients, prodromal constipation is linked to lower cognitive scores and higher apathy scores.
JOURNAL OF NEUROLOGY
(2021)
Review
Clinical Neurology
Maria Teresa Perinan, Kajsa Brolin, Sara Bandres-Ciga, Cornelis Blauwendraat, Christine Klein, Ziv Gan-Or, Andrew Singleton, Pilar Gomez-Garre, Maria Swanberg, Pablo Mir, Alastair Noyce
Summary: Parkinson's disease is a complex neurodegenerative condition caused by interactions between genetic and environmental factors. This article provides insights into the environmental modifiers of Parkinson's disease, discusses precedents from other neurological conditions, outlines genetic and environmental factors contributing to the disease, and reviews potential environmental modifiers affecting its severity.
ANNALS OF NEUROLOGY
(2022)
Review
Neurosciences
Tiago A. Mestre, Seyed-Mohammad Fereshtehnejad, Daniela Berg, Nicolaas Bohnen, Kathy Dujardin, Roberto Erro, Alberto J. Espay, Glenda Halliday, Jacobus J. van Hilten, Michele T. Hu, Beomseok Jeon, Christine Klein, Albert F. G. Leentjens, Johan Marinus, Brit Mollenhauer, Ronald Postuma, Rajasumi Rajalingam, Mayela Rodriguez-Violante, Tanya Simuni, D. James Surmeier, Daniel Weintraub, Michael P. McDermott, Michael Lawton, Connie Marras
Summary: The studies on PD subtypes have methodological shortcomings and questionable clinical applicability. Most studies did not achieve the highest rating on methodological quality checklists. The clinical importance of differences between subtypes and their potential treatment implications were rated poorly, indicating a need for new approaches that acknowledge individual-level heterogeneity and personalized medicine.
JOURNAL OF PARKINSONS DISEASE
(2021)
Article
Clinical Neurology
Jingru Ren, Ronggui Zhang, Chenxi Pan, Jianxia Xu, Haochen Sun, Ping Hua, Li Zhang, Wenbin Zhang, Pingyi Xu, Changyan Ma, Weiguo Liu
Summary: This study aimed to determine the frequency of GBA-related PD and the relationship between GBA variant severity and clinical characteristics in a large Chinese cohort. The results showed that GBA-PD is highly prevalent in the Chinese population, and patients carrying severe and complex variants have more severe symptoms.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Geriatrics & Gerontology
Hiroyo Yoshino, Yuanzhe Li, Kenya Nishioka, Kensuke Daida, Arisa Hayashida, Yuta Ishiguro, Daisuke Yamada, Nana Izawa, Katsunori Nishi, Noriko Nishikawa, Genko Oyama, Taku Hatano, Shinichiro Nakamura, Asako Yoritaka, Yumiko Motoi, Manabu Funayama, Nobutaka Hattori
Summary: This study investigated the prevalence and genotype-phenotype correlations of parkin RBR E3 ubiquitin protein ligase (PRKN) variants in Parkinson's disease (PD). The findings revealed that PRKN variants were associated with susceptibility to PD, and some of the variants were novel. Additionally, patients with two-allele had a younger age of onset, were more likely to have normal myocardial scintigraphy results, and showed exacerbation over the course of the disease.
NEUROBIOLOGY OF AGING
(2022)
Article
Genetics & Heredity
Fangzhi Jia, Avi Fellner, Kishore Raj Kumar
Summary: Parkinson's disease can be caused by a single pathogenic variant, but studying the genetic factors can provide important insights into the disease. This review discusses the different genetic forms, including their genotype, phenotype, pathophysiology, and geographic and ethnic distribution. It also highlights the influence of ethnicity and geography on monogenic Parkinson's disease and the need for global efforts to identify new candidate genes.
Review
Geriatrics & Gerontology
Jaroslaw Dulski, Ryan J. Uitti, Owen A. Ross, Zbigniew K. Wszolek
Summary: The heterogeneity of Parkinson's disease has been recognized for a long time, and its pathophysiological foundations are still unclear. Genetic factors may play a crucial role in understanding the subtypes of Parkinson's disease and successful gene therapy. This review discusses the current state of knowledge on the genetic architecture of Parkinson's disease subtypes, including monogenic and polygenic risk factors.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Hematology
Dominique P. M. S. M. Maas, Ferdows Atiq, Nicole M. A. Blijlevens, Paul P. T. Brons, Sandy Krouwel, Britta A. P. Laros-van Gorkom, Frank W. G. Leebeek, Laurens Nieuwenhuizen, Selene C. M. Schoormans, Annet Simons, Danielle Meijer, Waander L. van Heerde, Saskia E. M. Schols
Summary: This study reveals the clinical and laboratory characteristics of genetically confirmed VWD type 2M patients, showing that they have a relatively mild clinical phenotype, except for bleeding after surgery and delivery. Laboratory phenotype varies and depends on the underlying genetic variant. The addition of genotyping to the current phenotypic characterization may improve diagnosis and classification of VWD.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Clinical Neurology
Tyler Rehbein, Tong Tong Wu, Simona Treidler, Davide Pareyson, Richard Lewis, Sabrina W. Yum, Brett A. McCray, Sindhu Ramchandren, Joshua Burns, Jun Li, Richard S. Finkel, Steven S. Scherer, Stephan Zuchner, Michael E. Shy, Mary M. Reilly, David N. Herrmann
Summary: Recessive SH3TC2 variants cause CMT4C, a disease with variable clinical characteristics. Longitudinal analysis of 56 patients showed that CMTES and CMTES-R scores were moderately responsive to change over 3 years, indicating their usefulness in assessing disease progression.
Article
Clinical Neurology
Gabriel Torrealba-Acosta, Eric Yu, Tanya Lobo-Prada, Javier Ruiz-Martinez, Ana Gorostidi-Pagola, Ziv Gan-Or, Kenneth Carazo-Cespedes, Jean-Francois Trempe, Ignacio F. Mata, Jaime Fornaguera-Trias
Summary: Most research on PD has focused on European populations, resulting in underrepresentation of Latin American populations. This study characterized PD patients of Costa Rican origin and sequenced genes associated with familial PD and atypical parkinsonism. Physical activity correlated with better motor performance, while increased education was associated with better cognitive function. No association was found between tested genes and PD, but rare variants in LRRK2 and non-synonymous GBA variants were identified.
FRONTIERS IN NEUROLOGY
(2021)
Article
Clinical Neurology
Aliyah Glover, Lakshmi Pillai, Rohit Dhall, Tuhin Firmani
Summary: Olfactory dysfunction in Parkinson's disease can be detected before motor symptoms, and a specific pattern of odorant identification on the UPSIT may discriminate between patients with and without freezing of gait. Freezers showed more severe hyposmia and had significantly worse identification of nine odors compared to non-freezers. A 3-odorant score can effectively categorize freezers and non-freezers with similar sensitivity and specificity to short odorant Parkinson's disease identification batteries.
FRONTIERS IN NEUROLOGY
(2021)
Review
Biochemistry & Molecular Biology
Marina N. Karpenko, Zamira M. Muruzheva, Ekaterina Yu. Ilyechova, Polina S. Babich, Ludmila V. Puchkova
Summary: In the last 15 years, the relationship between copper imbalance and the development of idiopathic Parkinson's disease (PD) has been extensively studied. Despite the large number of papers on the subject, the correlation between copper status and PD development is still debated. Based on published literature, meta-analysis, and new research findings, it is clear that there is a weak connection between the number of copper atoms and the development of PD symptoms. This work also discusses the link between inborn errors related to copper metabolism and the risk of developing PD.
Article
Gastroenterology & Hepatology
Li Wang, Yi-Ling Qiu, Hong-Mei Xu, Jing Zhu, Shuang-Jie Li, Wen-Xian OuYang, Yong-Feng Yang, Yi Lu, Xin-Bao Xie, Qing-He Xing, Jian-She Wang
Summary: The phenotype of MYO5B deficiency is associated with MYO5B genotypes, particularly null variants or affected domains. The severity of intestinal manifestation and cholestasis in FIC patients is correlated with specific variants of the MYO5B gene. Missense/in-frame variants affecting non-motor regions and IQ motifs in MYO5B are more common in FIC patients compared to MVID patients.
LIVER INTERNATIONAL
(2022)
Article
Cardiac & Cardiovascular Systems
Jonas W. Bartstra, Sara Risseeuw, Pim A. de Jong, Bram van Os, Lianne Kalsbeek, Chris Mol, Annette F. Baas, Shana Verschuere, Olivier Vanakker, Ralph J. Florijn, Jeroen Hendrikse, Willem Mali, Saskia Imhof, Jeannette Ossewaarde-van Norel, Redmer van Leeuwen, Wilko Spiering
Summary: The study revealed that PXE patients with a mixed genotype showed less severe arterial and ophthalmological phenotypes compared to patients with two truncating variants in the ABCC6 gene. Further research into environmental and genetic modifiers may help explain the unexplained phenotypic variability.
Article
Clinical Neurology
Joshua Stevenson-Hoare, Amanda Heslegrave, Ganna Leonenko, Dina Fathalla, Eftychia Bellou, Lauren Luckcuck, Rachel Marshall, Rebecca Sims, Bryan Paul Morgan, John Hardy, Bart de Strooper, Julie Williams, Henrik Zetterberg, Valentina Escott-Price
Summary: Plasma biomarkers for Alzheimer's disease-related pathologies have made significant progress in recent years, with well-validated blood tests available for the detection of amyloid and tau pathology, as well as neurodegeneration and astrocytic activation. This study demonstrates that a combination of five plasma biomarkers, along with genetic variants associated with these biomarkers, can be used to accurately diagnose and predict the onset of Alzheimer's disease.
Article
Clinical Neurology
Kimberley J. Billingsley, Jinhui Ding, Pilar Alvarez Jerez, Anastasia Illarionova, Kristin Levine, Francis P. Grenn, Mary B. Makarious, Anni Moore, Daniel Vitale, Xylena Reed, Dena Hernandez, Ali Torkamani, Mina Ryten, John Hardy, Ruth W. Chia, Sonja J. Scholz, Bryan L. Traynor, Clifton J. Dalgard, Debra Ehrlich, Toshiko Tanaka, Luigi G. Ferrucci, Thomas E. Beach, Geidy P. Serrano, John J. Quinn, Vivien Bubb, Ryan L. Collins, Xuefang Zhao, Mark Walker, Emma Pierce-Hoffman, Harrison E. Brand, Michael Talkowski, Bradford Casey, Mark R. Cookson, Androo A. Markham, Mike Nalls, Medhat Mahmoud, Fritz J. Sedlazeck, Cornelis Blauwendraat, J. Raphael B. Gibbs, Andrew Singleton
Summary: By studying the genetic factors of Parkinson's disease, three structural variants associated with the risk of the disease have been discovered. This is the most comprehensive study to date of the contribution of structural variants to the genetic risk of Parkinson's disease.
ANNALS OF NEUROLOGY
(2023)
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
Clinical Neurology
Raquel Real, Alejandro Martinez-Carrasco, Regina H. Reynolds, Michael A. Lawton, Manuela M. X. Tan, Maryam Shoai, Jean-Christophe Corvol, Mina Ryten, Catherine Bresner, Leon Hubbard, Alexis Brice, Suzanne Lesage, Johann Faouzi, Alexis Elbaz, Fanny Artaud, Nigel Williams, Michele T. M. Hu, Yoav Ben-Shlomo, Donald G. Grosset, John Hardy, Huw R. Morris
Summary: Researchers performed a genome-wide survival study on almost 4000 Parkinson's disease patients and identified new genetic loci associated with faster progression to Parkinson's disease dementia, including the LRP1B receptor. Parkinson's disease is a common neurodegenerative disorder, and cognitive impairment and dementia are important features in the later stages of the disease. The genetic basis for the heterogeneity in cognitive decline among Parkinson's disease patients is not fully understood.
Article
Clinical Neurology
Katherine Lloyd, Michael Lawton, Alan Whone
Summary: This study describes the increasingly prevalent pracoff-state dyskinesia during a trophic factor study, suggesting that GDNF may enable recovery of endogenous dopamine release in advanced Parkinson's disease.
MOVEMENT DISORDERS
(2023)
Article
Biology
Nirmal Verma, Gopal Viswanathan Velmurugan, Edric Winford, Han Coburn, Deepak Kotiya, Noah Leibold, Laura Radulescu, Sanda Despa, Kuey C. Chen, Linda J. Van Eldik, Peter T. Nelson, Donna M. Wilcock, Gregory A. Jicha, Ann M. Stowe, Larry B. Goldstein, David K. Powel, Jeffrey H. Walton, Manuel F. Navedo, Matthew A. Nystoriak, Andrew J. Murray, Geert Jan Biessels, Claire Troakes, Henrik Zetterberg, John Hardy, Tammaryn Lashley, Florin Despa
Summary: Impairment of vascular pathways contributes to Alzheimer's disease. Blood amylin secreted from the pancreas perturbs cerebral A beta clearance, leading to amylin and A beta co-deposits in the brain microvasculature. Altering bloodborne amylin could potentially reduce cerebrovascular amylin deposits and A beta pathology.
COMMUNICATIONS BIOLOGY
(2023)
Letter
Clinical Neurology
John Hardy, Catherine Mummery
Editorial Material
Clinical Neurology
John Hardy, Catherine Mummery
Review
Clinical Neurology
Tiago F. Outeiro, Roy N. Alcalay, Angelo Antonini, Johannes Attems, Vincenzo Bonifati, Francisco Cardoso, Marie-Francoise Chesselet, John Hardy, Graziella Madeo, Ian McKeith, Brit Mollenhauer, Darren J. Moore, Olivier Rascol, Michael G. Schlossmacher, Hermona Soreq, Leonidas Stefanis, Joaquim J. Ferreira
Summary: Parkinson's disease is a complex syndrome with inconsistent definitions in various domains. To make breakthroughs in treatment, it is important to integrate the diverse disciplines and define the endophenotypes of typical PD accurately.
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Harald Hampel, Yan Hu, John Hardy, Kaj Blennow, Christopher Chen, George Perry, Seung Hyun Kim, Victor L. Villemagne, Paul Aisen, Michele Vendruscolo, Takeshi Iwatsubo, Colin L. Masters, Min Cho, Lars Lannfelt, Jeffrey L. Cummings, Andrea Vergallo
Summary: This summary reviews the evidence supporting the role of the amyloid-b (Ab) pathway in Alzheimer's disease (AD) and emphasizes the importance of targeting this pathway in early stages of the disease. Understanding and targeting the A beta pathway can lead to better therapeutic outcomes and management of AD.
NEURODEGENERATIVE DISEASE MANAGEMENT
(2023)
Article
Neurosciences
Lindsey Sinclair, Michael A. Lawton, Jennifer C. Palmer, Clive G. Ballard
Summary: Depression in individuals with Alzheimer's disease (AD) is common and difficult to treat, and the reasons for its occurrence are still unclear. Previous depression is the strongest risk factor for depression in AD.
JOURNAL OF ALZHEIMERS DISEASE REPORTS
(2023)
Article
Medicine, General & Internal
Harriet A. Ball, Elizabeth Coulthard, Mark Fish, Antony Bayer, John Gallacher, Yoav Ben-Shlomo
Summary: This study examines the association between subjective cognitive decline (sSCD) and objective cognition, finding a weak correlation between the two. Older age, poor sleep quality, and higher anxiety are independent predictors of sSCD. The study suggests that sSCD, in the absence of objective decline, may be an example of poor meta-cognition and a potential driver for functional cognitive disorder (FCD).
Review
Public, Environmental & Occupational Health
Mark Parkinson, Cormac Ryan, Leah Avery, Annette Hand, Bhanu Ramaswamy, Julie Jones, Fiona Lindop, Monty Silverdale, Katherine Baker, Jenni Naisby
Summary: This scoping review aims to examine the available evidence on pain management in Parkinson's, with a focus on behavioural interventions, resources, and professional support for self-management. The review will analyze both quantitative and qualitative data to identify the characteristics of support for pain management, orientation of approaches, and behavior change components and outcomes.
INTERNATIONAL JOURNAL FOR EQUITY IN HEALTH
(2023)
Article
Clinical Neurology
Riccardo Ronco, Cecilia Perini, Riccardo Curro, Natalia Dominik, Stefano Facchini, Alice Gennari, Roberto Simone, Skye Stuart, Sara Nagy, Elisa Vegezzi, Ilaria Quartesan, Amar El-Saddig, Timothy Lavin, Arianna Tucci, Agnieszka Szymura, Luiz Eduardo Novis De Farias, Alexander Gary, Megan Delfeld, Priscilla Kandikatla, Nifang Niu, Sanjukta Tawde, Joseph Shaw, James Polke, Mary M. Reilly, Nick W. Wood, Emmanuele Crespan, Christopher Gomez, Jin Yun Helen Chen, Jeremy Dan Schmahmann, David Gosal, Henry Houlden, Soma Das, Andrea Cortese
Summary: This study expands the genotypic spectrum of CANVAS by identifying sequence variants in the RFC1-coding region. The findings provide diagnostic recommendations for CANVAS and shed further light on its pathogenesis.