Postural instability and resulting falls are major factors determining quality of life, morbidity, and mortality in individuals with Parkinson’s disease (PD). A better understanding of balance impairments would improve management of balance dysfunction and prevent falls in patients with PD. The effects of bradykinesia, rigidity, impaired proprioception, freezing of gait and attention on postural stability in patients with idiopathic PD have been well characterized in laboratory studies. The purpose of this review is to systematically summarize the types of balance impairments contributing to postural instability in people with PD.
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Progressive supranuclear palsy (PSP) is a neurodegenerative syndrome that is clinically characterized by progressive postural instability, supranuclear gaze palsy, parkinsonism and cognitive decline. Pathologically, diagnosis of PSP is based on characteristic features, such as neurofibrillary tangles, neutrophil threads, tau-positive astrocytes and their processes in basal ganglia and brainstem, and the accumulation of 4 repeat tau protein. PSP is generally recognized as a sporadic disorder; however, understanding of genetic background of PSP has been expanding rapidly. Here we review relevant publications to outline the genetics of PSP. Although only small number of familial PSP cases have been reported, the recognition of familial PSP has been increasing. In some familial cases of clinically probable PSP, PSP pathologies were confirmed based on NINDS neuropathological diagnostic criteria. Several mutations in MAPT, the gene that causes a form of familial frontotemporal lobar degeneration with tauopathy, have been identified in both sporadic and familial PSP cases. The H1 haplotype of MAPT is a risk haplotype for PSP, and within H1, a sub-haplotype (H1c) is associated with PSP. A recent genome-wide association study on autopsyproven PSP revealed additional PSP risk alleles in STX6 and EIF2AK3. Several heredodegenerative parkinsonian disorders are referred to as PSP-look-alikes because their clinical phenotype, but not their pathology, mimics PSP. Due to the fast development of genomics and bioinformatics, more genetic factors related to PSP are expected to be discovered. Undoubtedly, these studies will provide a better understanding of the pathogenesis of PSP and clues for developing therapeutic strategies.
Identification of Genetic Variants in Progressive Supranuclear Palsy in Southeast Asia Adeline Su Lyn Ng, Ai Huey Tan, Yi Jayne Tan, Jia Lun Lim, Michelle Mulan Lian, Alfand Marl Dy Closas, Azlina Ahmad‐Annuar, Shanthi Viswanathan, Yuen Kang Chia, Jia Nee Foo, Weng Khong Lim, Eng‐King Tan, Shen‐Yang Lim Movement Disorders.2024;[Epub] CrossRef
Genetic Architecture of Primary Tauopathies Daniel Gallo, Agustín Ruiz, Pascual Sánchez-Juan Neuroscience.2023; 518: 27. CrossRef
Direct and Indirect Effects of Filamin A on Tau Pathology in Neuronal Cells Stéphanie Levert, Julie Pilliod, Étienne Aumont, Sandrine Armanville, Cyntia Tremblay, Frédéric Calon, Nicole Leclerc Molecular Neurobiology.2023; 60(2): 1021. CrossRef
Identification of phosphorylated tau protein interactors in progressive supranuclear palsy (PSP) reveals networks involved in protein degradation, stress response, cytoskeletal dynamics, metabolic processes, and neurotransmission Rowan A. W. Radford, Stephanie L. Rayner, Paulina Szwaja, Marco Morsch, Flora Cheng, Tianyi Zhu, Jocelyn Widagdo, Victor Anggono, Dean L. Pountney, Roger Chung, Albert Lee Journal of Neurochemistry.2023; 165(4): 563. CrossRef
Pathomechanisms of cognitive impairment in progressive supranuclear palsy Kurt A. Jellinger Journal of Neural Transmission.2023; 130(4): 481. CrossRef
Differential Diagnosis of Rare Subtypes of Progressive Supranuclear Palsy and PSP-Like Syndromes—Infrequent Manifestations of the Most Common Form of Atypical Parkinsonism Patrycja Krzosek, Natalia Madetko, Anna Migda, Bartosz Migda, Dominika Jaguś, Piotr Alster Frontiers in Aging Neuroscience.2022;[Epub] CrossRef
Characterisation of the Function of a SINE-VNTR-Alu Retrotransposon to Modulate Isoform Expression at the MAPT Locus Alexander Fröhlich, Abigail L. Pfaff, Vivien J. Bubb, Sulev Koks, John P. Quinn Frontiers in Molecular Neuroscience.2022;[Epub] CrossRef
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MAPT gene mutation in familiar progressive supranuclear palsy, a case report M. Rodríguez, H. Kreinter, N. Zapa, O. Oliveros, C. Jiménez Neurology Perspectives.2022; 2(3): 184. CrossRef
Investigational therapeutics for the treatment of progressive supranuclear palsy David G Coughlin, Irene Litvan Expert Opinion on Investigational Drugs.2022; 31(8): 813. CrossRef
Mass spectrometry‐based proteomics analysis of human globus pallidus from progressive supranuclear palsy patients discovers multiple disease pathways Yura Jang, Thujitha Thuraisamy, Javier Redding‐Ochoa, Olga Pletnikova, Juan C. Troncoso, Zhen Zhang, Liana S. Rosenthal, Ted M. Dawson, Alexander Y. Pantelyat, Chan Hyun Na Clinical and Translational Medicine.2022;[Epub] CrossRef
Reference SVA insertion polymorphisms are associated with Parkinson’s Disease progression and differential gene expression Abigail L. Pfaff, Vivien J. Bubb, John P. Quinn, Sulev Koks npj Parkinson's Disease.2021;[Epub] CrossRef
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Heavy metals contaminating the environment of a progressive supranuclear palsy cluster induce tau accumulation and cell death in cultured neurons Carolina Alquezar, Jessica B. Felix, Elizabeth McCandlish, Brian T. Buckley, Dominique Caparros-Lefebvre, Celeste M. Karch, Lawrence I. Golbe, Aimee W. Kao Scientific Reports.2020;[Epub] CrossRef
LRP10 variants in progressive supranuclear palsy Leonie J.M. Vergouw, Shamiram Melhem, Laura Donker Kaat, Wang Z. Chiu, Demy J.S. Kuipers, Guido Breedveld, Agnita J.W. Boon, Li-San Wang, Adam C. Naj, Elizabeth Mlynarksi, Laura Cantwell, Marialuisa Quadri, Owen A. Ross, Dennis W. Dickson, Gerard D. Schel Neurobiology of Aging.2020;[Epub] CrossRef
Neuro-ophthalmology in the Geriatric Eye Subhan Tabba, Yi-Hsien Yeh, Ashwini Kini, Bayan Al Othman, Andrew G Lee US Ophthalmic Review.2020; 13(1): 30. CrossRef
Genetic Risk Factors for Essential Tremor: A Review Vasileios Siokas, Athina-Maria Aloizou, Zisis Tsouris, Ioannis Liampas, Paraskevi Aslanidou, Metaxia Dastamani, Alexandros G. Brotis, Dimitrios P. Bogdanos, Georgios M. Hadjigeorgiou, Efthimios Dardiotis Tremor and Other Hyperkinetic Movements.2020; 10: 4. CrossRef
PSP-FTD Complex: A Possible Variant of PSP Sunil Pradhan, Ruchika Tandon American Journal of Alzheimer's Disease & Other Dementiasr.2020; 35: 153331752092238. CrossRef
Microglial Activation and Inflammation as a Factor in the Pathogenesis of Progressive Supranuclear Palsy (PSP) Piotr Alster, Natalia Madetko, Dariusz Koziorowski, Andrzej Friedman Frontiers in Neuroscience.2020;[Epub] CrossRef
Tau at the interface between neurodegeneration and neuroinflammation Alessandro Didonna Genes & Immunity.2020; 21(5): 288. CrossRef
Efficiency of Transcranial Magnetic Stimulation in Progressive Supranuclear Palsy: Estimation Using Goniometry and Dinamometry K. A. Major, Z. Zs. Major, R. Craciunas, G. Carbone, C. Vaida, D. L. Pîslă Neurophysiology.2019; 51(1): 57. CrossRef
Four-repeat tauopathies Thomas W. Rösler, Amir Tayaranian Marvian, Matthias Brendel, Niko-Petteri Nykänen, Matthias Höllerhage, Sigrid C. Schwarz, Franziska Hopfner, Thomas Koeglsperger, Gesine Respondek, Kerstin Schweyer, Johannes Levin, Victor L. Villemagne, Henryk Barthel, Os Progress in Neurobiology.2019; 180: 101644. CrossRef
One decade ago, one decade ahead in progressive supranuclear palsy Maria Stamelou, Nikolaos Giagkou, Günter U Höglinger Movement Disorders.2019; 34(9): 1284. CrossRef
The genetic and clinico‐pathological profile of early‐onset progressive supranuclear palsy Edwin Jabbari, John Woodside, Manuela M.X. Tan, Nicola Pavese, Oliver Bandmann, Boyd C.P. Ghosh, Luke A. Massey, Erica Capps, Tom T. Warner, Andrew J. Lees, Tamas Revesz, Janice L. Holton, Nigel M. Williams, Donald G. Grosset, Huw R. Morris Movement Disorders.2019; 34(9): 1307. CrossRef
Tau-Induced Pathology in Epilepsy and Dementia: Notions from Patients and Animal Models Marina Sánchez, Ana García-Cabrero, Gentzane Sánchez-Elexpuru, Daniel Burgos, José Serratosa International Journal of Molecular Sciences.2018; 19(4): 1092. CrossRef
Replication of progressive supranuclear palsy genome-wide association study identifies SLCO1A2 and DUSP10 as new susceptibility loci Monica Y. Sanchez-Contreras, Naomi Kouri, Casey N. Cook, Daniel J. Serie, Michael G. Heckman, NiCole A. Finch, Richard J. Caselli, Ryan J. Uitti, Zbigniew K. Wszolek, Neill Graff-Radford, Leonard Petrucelli, Li-San Wang, Gerard D. Schellenberg, Dennis W. Molecular Neurodegeneration.2018;[Epub] CrossRef
Improving Mouse Models for Dementia. Are All the Effects in Tau Mouse Models Due to Overexpression? Zelah Joel, Pablo Izquierdo, Dervis A. Salih, Jill C. Richardson, Damian M. Cummings, Frances A. Edwards Cold Spring Harbor Symposia on Quantitative Biology.2018; 83: 151. CrossRef
Signature of an aggregation-prone conformation of tau Neil A. Eschmann, Elka R. Georgieva, Pritam Ganguly, Peter P. Borbat, Maxime D. Rappaport, Yasar Akdogan, Jack H. Freed, Joan-Emma Shea, Songi Han Scientific Reports.2017;[Epub] CrossRef
Chronic traumatic encephalopathy-integration of canonical traumatic brain injury secondary injury mechanisms with tau pathology Jacqueline R. Kulbe, Edward D. Hall Progress in Neurobiology.2017; 158: 15. CrossRef
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Gene expression, methylation and neuropathology correlations at progressive supranuclear palsy risk loci Mariet Allen, Jeremy D. Burgess, Travis Ballard, Daniel Serie, Xue Wang, Curtis S. Younkin, Zhifu Sun, Naomi Kouri, Saurabh Baheti, Chen Wang, Minerva M. Carrasquillo, Thuy Nguyen, Sarah Lincoln, Kimberly Malphrus, Melissa Murray, Todd E. Golde, Nathan D. Acta Neuropathologica.2016; 132(2): 197. CrossRef
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Genetic and Transcriptomic Profiles of Inflammation in Neurodegenerative Diseases: Alzheimer, Parkinson, Creutzfeldt-Jakob and Tauopathies Irene López González, Paula Garcia-Esparcia, Franc Llorens, Isidre Ferrer International Journal of Molecular Sciences.2016; 17(2): 206. CrossRef
Genetic Disorders with Tau Pathology: A Review of the Literature and Report of Two Patients with Tauopathy and Positive Family Histories Pawel Tacik, Monica Sanchez-Contreras, Rosa Rademakers, Dennis W. Dickson, Zbigniew K. Wszolek Neurodegenerative Diseases.2016; 16(1-2): 12. CrossRef
Objective Gender differences are a well-known clinical characteristic of Parkinson’s disease (PD). In-vivo imaging studies demonstrated that women have greater striatal dopamine transporter (DAT) activity than do men, both in the normal population and in PD patients. We hypothesize that women exhibit more rapid aging-related striatal DAT reduction than do men, as the potential neuroprotective effect of estrogen wanes with age.
Methods This study included 307 de novo PD patients (152 men and 155 women) who underwent DAT scans for an initial diagnostic work-up. Gender differences in age-related DAT decline were assessed in striatal sub-regions using linear regression analysis.
Results Female patients exhibited greater DAT activity compared with male patients in all striatal sub-regions. The linear regression analysis revealed that age-related DAT decline was greater in the anterior and posterior caudate, and the anterior putamen in women compared with men; we did not observe this difference in other sub-regions.
Conclusions This study demonstrated the presence of gender differences in age-related DAT decline in striatal sub-regions, particularly in the antero-dorsal striatum, in patients with PD, presumably due to aging-related decrease in estrogen. Because this difference was not observed in the sensorimotor striatum, this finding also suggests that women may not have a greater capacity to tolerate PD pathogenesis than do men.
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