Journal of Movement Disorders

Review Articles

α-Synuclein: A Promising Biomarker for Parkinson’s Disease and Related Disorders: Taku Hatano, Ayami Okuzumi, Gen Matsumoto, Tsunemi Taiji, Nobutaka Hattori; Received March 22, 2024 Accepted April 9, 2024 Published online April 9, 2024; DOI: https://doi.org/10.14802/jmd.24075 [Accepted]

380 View
89 Download

Abstract PDF: Mutations in the SNCA gene, which encodes α-synuclein (α-syn), play a key role in the development of genetic Parkinson’s disease (PD). α-Syn is a major component of Lewy bodies in PD and glial cytoplasmic inclusions in multiple system atrophy (MSA). Rapid eye movement sleep behavior disorder (RBD) patients often progress to PD, dementia with Lewy bodies (DLB), or MSA, collectively known as α-synucleinopathies. The loss of dopaminergic neurons with Lewy bodies precedes motor dysfunction in these diseases, but the mechanisms of neurodegeneration due to α-syn aggregation are poorly understood. Monitoring α-syn aggregation in vivo could serve as a diagnostic biomarker and help elucidate the pathogenesis, necessitating a simple and accurate detection method. Seed amplification assays (SAAs), such as real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA), are used to detect small amounts of abnormally structured α-syn protofibrils, which are central to aggregation. These methods are promising for the early diagnosis of α-synucleinopathy. Differences in α-syn filament structures between α-synucleinopathies, observed through transmission electron microscopy and cryo-electron microscopy, suggest their role in the pathogenesis of neurodegeneration. SAAs may differentiate between subtypes of α-synucleinopathy and other diseases. Efforts are also being made to identify α-syn from blood using various methods. This review introduces body fluid α-syn biomarkers based on pathogenic α-syn seeds, which are expected to redefine α-synucleinopathy diagnosis and staging, improving clinical research accuracy and facilitating biomarker development.

Ultrastructures of α-Synuclein Filaments in Synucleinopathy Brains and Experimental Models: Airi Tarutani, Masato Hasegawa; J Mov Disord. 2024;17(1):15-29. Published online November 22, 2023; DOI: https://doi.org/10.14802/jmd.23213

1,310 View
146 Download

Abstract PDF: Intracellular α-synuclein (α-syn) inclusions are a neuropathological hallmark of Lewy body disease (LBD) and multiple system atrophy (MSA), both of which are termed synucleinopathies. LBD is defined by Lewy bodies and Lewy neurites in neurons, while MSA displays glial cytoplasmic inclusions in oligodendrocytes. Pathological α-syn adopts an ordered filamentous structure with a 5–10 nm filament diameter, and this conformational change has been suggested to be involved in the disease onset and progression. Synucleinopathies also exhibit characteristic ultrastructural and biochemical properties of α-syn filaments, and α-syn strains with distinct conformations have been identified. Numerous experimental studies have supported the idea that pathological α-syn self-amplifies and spreads throughout the brain, during which processes the conformation of α-syn filaments may drive the disease specificity. In this review, we summarize the ultrastructural features and heterogeneity of α-syn filaments in the brains of patients with synucleinopathy and in experimental models of seeded α-syn aggregation.

Multiple System Atrophy: Advances in Diagnosis and Therapy: Hirohisa Watanabe, Sayuri Shima, Yasuaki Mizutani, Akihiro Ueda, Mizuki Ito; J Mov Disord. 2023;16(1):13-21. Published online December 20, 2022; DOI: https://doi.org/10.14802/jmd.22082

3,606 View
410 Download
2 Web of Science
2 Crossref

Abstract PDF

This review summarizes improvements in understanding the pathophysiology and early clinical symptoms of multiple system atrophy (MSA) and advancements in diagnostic methods and disease-modifying therapies for the condition. In 2022, the Movement Disorder Society proposed new diagnostic criteria to develop disease-modifying therapies and promote clinical trials of MSA since the second consensus was proposed in 2008. Regarding pathogenesis, cutting-edge findings have accumulated on the interactions of α-synuclein, neuroinflammation, and oligodendroglia with neurons. In neuroimaging, introducing artificial intelligence, machine learning, and deep learning has notably improved diagnostic accuracy and individual analyses. Advancements in treatment have also been achieved, including immunotherapy therapy against α-synuclein and serotonin-targeted and mesenchymal stem cell therapies, which are thought to affect several aspects of the disease, including neuroinflammation. The accelerated progress in clarifying the pathogenesis of MSA over the past few years and the development of diagnostic techniques for detecting early-stage MSA are expected to facilitate the development of disease-modifying therapies for one of the most intractable neurodegenerative diseases.

Citations

Citations to this article as recorded by

A Blinded Evaluation of Brain Morphometry for Differential Diagnosis of Atypical Parkinsonism
Kazuya Kawabata, Florian Krismer, Beatrice Heim, Anna Hussl, Christoph Mueller, Christoph Scherfler, Elke R. Gizewski, Klaus Seppi, Werner Poewe
Movement Disorders Clinical Practice.2024; 11(4): 381. CrossRef
The potential of phosphorylated α‐synuclein as a biomarker for the diagnosis and monitoring of multiple system atrophy
Toufik Abdul‐Rahman, Ranferi Eduardo Herrera‐Calderón, Arjun Ahluwalia, Andrew Awuah Wireko, Tomas Ferreira, Joecelyn Kirani Tan, Maximillian Wolfson, Shankhaneel Ghosh, Viktoriia Horbas, Vandana Garg, Asma Perveen, Marios Papadakis, Ghulam Md Ashraf, Ath
CNS Neuroscience & Therapeutics.2024;[Epub] CrossRef

Diagnostic Criteria for Dementia with Lewy Bodies: Updates and Future Directions: Masahito Yamada, Junji Komatsu, Keiko Nakamura, Kenji Sakai, Miharu Samuraki-Yokohama, Kenichi Nakajima, Mitsuhiro Yoshita; J Mov Disord. 2020;13(1):1-10. Published online November 8, 2019; DOI: https://doi.org/10.14802/jmd.19052

25,933 View
1,691 Download
40 Web of Science
48 Crossref

Abstract PDF

The aim of this article is to describe the 2017 revised consensus criteria for the clinical diagnosis of dementia with Lewy bodies (DLB) with future directions for the diagnostic criteria. The criteria for the clinical diagnosis of probable and possible DLB were first published as the first consensus report in 1996 and were revised in the third consensus report in 2005. After discussion at the International DLB Conference in Fort Lauderdale, Florida, USA, in 2015, the International DLB Consortium published the fourth consensus report including the revised consensus criteria in 2017. The 2017 revised criteria clearly distinguish between clinical features and diagnostic biomarkers. Significant new information about previously reported aspects of DLB has been incorporated, with increased diagnostic weighting given to rapid eye movement (REM) sleep behavior disorder (RBD) and iodine-123-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. Future directions include the development of the criteria for early diagnosis (prodromal DLB) and the establishment of new biomarkers that directly indicate Lewy-related pathology, including α-synuclein imaging, biopsies of peripheral tissues (skin, etc.) for the demonstration of α-synuclein deposition, and biochemical markers (cerebrospinal fluid/blood), as well as the pathological evaluation of the sensitivity and specificity of the 2017 revised diagnostic criteria. In conclusion, the revised consensus criteria for the clinical diagnosis of DLB were reported with the incorporation of new information about DLB in 2017. Future directions include the development of the criteria for early diagnosis and the establishment of biomarkers directly indicative of Lewy-related pathology.

Citations

Citations to this article as recorded by

The Role of Electroconvulsive Therapy in the Treatment of Catatonia Associated With Lewy Body Dementia: A Case Report
Javeria Sahib Din, Thomas Boes, Ernesto Navarro Garcia, Hiba Al-Rubaye
Cureus.2024;[Epub] CrossRef
α-Synuclein pathology from the body to the brain: so many seeds so close to the central soil
Yunying Yang, Zhentao Zhang
Neural Regeneration Research.2024; 19(7): 1463. CrossRef
Suspecting Non-Alzheimer’s Pathologies and Mixed Pathologies: A Comparative Study Between Brain Metabolism and Tau Images
Vincent Malotaux, Lise Colmant, Lisa Quenon, Lara Huyghe, Thomas Gérard, Laurence Dricot, Adrian Ivanoiu, Renaud Lhommel, Bernard Hanseeuw
Journal of Alzheimer's Disease.2024; 97(1): 421. CrossRef
Supercomplex formation of mitochondrial respiratory chain complexes in leukocytes from patients with neurodegenerative diseases
Tsukasa Hara, Ryosuke Amagai, Ryuji Sakakibara, Ayako Okado-Matsumoto
The Journal of Biochemistry.2024; 175(3): 289. CrossRef
Latest advances in mechanisms of epileptic activity in Alzheimer’s disease and dementia with Lewy Bodies
Mariane Vicente, Kwaku Addo-Osafo, Keith Vossel
Frontiers in Neurology.2024;[Epub] CrossRef
The clinical diagnosis of Parkinson's disease
Renato P. Munhoz, Vitor Tumas, José Luiz Pedroso, Laura Silveira-Moriyama
Arquivos de Neuro-Psiquiatria.2024; 82(06): 001. CrossRef
Identification of Potentially Repurposable Drugs for Lewy Body Dementia Using a Network-Based Approach
Megha Manoj, Siddarth Sowmyanarayan, Arjun V. Kowshik, Jhinuk Chatterjee
Journal of Molecular Neuroscience.2024;[Epub] CrossRef
Altered structural and functional connectivity in Posterior Cortical Atrophy and Dementia with Lewy bodies
Neha Atulkumar Singh, Austin W. Goodrich, Jonathan Graff-Radford, Mary M. Machulda, Irene Sintini, Arenn F. Carlos, Carling G. Robinson, Robert I. Reid, Val J. Lowe, Clifford R. Jack, Ronald C. Petersen, Bradley F. Boeve, Keith A. Josephs, Kejal Kantarci,
NeuroImage.2024; 290: 120564. CrossRef
Clinicopathological correlation of cerebrospinal fluid alpha‐synuclein seed amplification assay in a behavioral neurology autopsy cohort
Niyatee Samudra, D. Luke Fischer, Steven Lenio, Argentina Lario Lago, Peter A. Ljubenkov, Julio C. Rojas, William W. Seeley, Salvatore Spina, Adam M. Staffaroni, Jonathan Tablante, Fattin Wekselman, Jennifer Lamoureux, Luis Concha‐Marambio, Lea T. Grinber
Alzheimer's & Dementia.2024;[Epub] CrossRef
New insight of exercise on dementia; combinatory effects of physical and cognitive exercise
Hyo-Jeong Cha, Jun Hong Park, Changwan Hong
Molecular & Cellular Toxicology.2024;[Epub] CrossRef
Magnetic resonance imaging in the diagnosis of progressive supranuclear palsy: A case report and review of literature
Baraka Alphonce, Francisca Komanya, Mbelwa Bitesigilwe, John R. Meda, Azan Nyundo
Clinical Case Reports.2023;[Epub] CrossRef
Parkinson's disease fluid biomarkers for differential diagnosis of atypical parkinsonian syndromes
Jun Yang, Ayotimofe Idowu, Liana Rosenthal, Xiaobo Mao
Clinical and Translational Discovery.2023;[Epub] CrossRef
Neurofilament light chain is increased in the parahippocampal cortex and associates with pathological hallmarks in Parkinson’s disease dementia
Irene Frigerio, Max A. Laansma, Chen-Pei Lin, Emma J. M. Hermans, Maud M. A. Bouwman, John G. J. M. Bol, Yvon Galis-de Graaf, Dagmar H. Hepp, Annemieke J. M. Rozemuller, Frederik Barkhof, Wilma D. J. van de Berg, Laura E. Jonkman
Translational Neurodegeneration.2023;[Epub] CrossRef
Machine learning-based prediction of conversion coefficients for I-123 metaiodobenzylguanidine heart-to-mediastinum ratio
Koichi Okuda, Kenichi Nakajima, Chiemi Kitamura, Michael Ljungberg, Tetsuo Hosoya, Yumiko Kirihara, Mitsumasa Hashimoto
Journal of Nuclear Cardiology.2023; 30(4): 1630. CrossRef
Costs During the Last Five Years of Life for Patients with Clinical and Pathological Confirmed Diagnosis of Lewy Body Dementia and Alzheimer’s Disease
Carolyn W. Zhu, Yian Gu, Anton J. Kociolek, Kayri K. Fernandez, Stephanie Cosentino, Yaakov Stern
Journal of Alzheimer's Disease.2023; 92(2): 457. CrossRef
Early- and late-onset of isolated rapid eye movement sleep behavior disorder: A retrospective cohort study
Li Zhou, Bei Huang, Jing Wang, Steven WH. Chau, Joey WY. Chan, Jihui Zhang, Mandy WM. Yu, Jessie CC. Tsang, Shirley Xin Li, Vincent CT. Mok, Yun Kwok Wing, Yaping Liu
Sleep Medicine.2023;[Epub] CrossRef
Parkinson Disease Dementia Management: an Update of Current Evidence and Future Directions
Oliver Phillips, Debolina Ghosh, Hubert H. Fernandez
Current Treatment Options in Neurology.2023; 25(5): 93. CrossRef
Rapidly progressive dementia with severe insomnia: an unusual case of progressive supranuclear palsy mimicking dementia with Lewy bodies
Rae On Kim, Eun Ji Lee, Seong-Ik Kim, Sung-Hye Park, Kyum-Yil Kwon
Neurological Sciences.2023; 44(8): 2953. CrossRef
Significance of clinical symptoms and red flags in early differential diagnosis of Parkinson’s disease and atypical Parkinsonian syndromes
Nils Schröter, Thilo van Eimeren, Joseph Classen, Johannes Levin, Christoph Redecker, Martin Wolz, Lars Tönges
Journal of Neural Transmission.2023; 130(6): 839. CrossRef
Electroencephalography in young onset dementia
Casey W Brown, Huei-Yang Chen, Peter K Panegyres
BMC Neurology.2023;[Epub] CrossRef
Clinical trials in dementia with Lewy bodies: the evolving concept of co-pathologies, patient selection and biomarkers
Lucy L. Gibson, Carla Abdelnour, Joyce Chong, Clive Ballard, Dag Aarsland
Current Opinion in Neurology.2023; 36(4): 264. CrossRef
Coexistence of Posterior Cortical Atrophy and Parkinson’s Disease
Eun-Byul Ko, Il-Joong Hwang, Jung-Woo Kim, Dar-Eun Jung, Ju-Suk Lee, Sang-Won Yoo, Joong-Seok Kim
Journal of the Korean Neurological Association.2023; 41(3): 216. CrossRef
Toward a new nosology of neurodegenerative diseases
Manuel Menéndez‐González
Alzheimer's & Dementia.2023; 19(8): 3731. CrossRef
Autonomic dysfunction in dementia with Lewy bodies: Focusing on cardiovascular and respiratory dysfunction
Katsuyoshi Mizukami
Psychiatry and Clinical Neurosciences Reports.2023;[Epub] CrossRef
Beyond Strains: Molecular Diversity in Alpha-Synuclein at the Center of Disease Heterogeneity
Marcelina J. Wojewska, Maria Otero-Jimenez, Jose Guijarro-Nuez, Javier Alegre-Abarrategui
International Journal of Molecular Sciences.2023; 24(17): 13199. CrossRef
Case Study 6: The Diagnostic Challenge of a 75-Year-Old Man Who Had, Then Didn’t Have, Then Did Have Alzheimer’s Disease
Sergio A. Ramírez-Salazar, Cassie MacRae, Mel B. Feany, Michael Miller, Hyun-Sik Yang, Mary-Ellen Meadows, Scott M. McGinnis, David Silbersweig, Seth A. Gale, Kirk R. Daffner
The Journal of Neuropsychiatry and Clinical Neurosciences.2023; 35(4): 325. CrossRef
Cardiac 123I-Metaiodobenzylguanidine (MIBG) Scintigraphy in Parkinson’s Disease: A Comprehensive Review
Jamir Pitton Rissardo, Ana Letícia Fornari Caprara
Brain Sciences.2023; 13(10): 1471. CrossRef
A Unique Perspective on Lead Compounds for Dementia with the Lewy Body
Menaka Subramani, Amuthalakshmi Sivaperuman, Ramalakshmi Natarajan, Keerthana Dhinakaran
Medicinal Chemistry.2023; 19(10): 946. CrossRef
Three-Dimensional Heart Segmentation and Absolute Quantitation of Cardiac ¹²³I-metaiodobenzylguanidine Sympathetic Imaging Using SPECT/CT
Shintaro Saito, Kenichi Nakajima, Takayuki Shibutani, Hiroshi Wakabayashi, Hiroto Yoneyama, Takahiro Konishi, Hiroshi Mori, Aki Takata, Seigo Kinuya
Annals of Nuclear Cardiology.2023; 9(1): 61. CrossRef
Comparison of Taiwanese and European Calibration Factors for Heart-to-Mediastinum Ratio in Multicenter ¹²³I-mIBG Phantom Studies
Koichi Okuda, Kenichi Nakajima, Guang-Uei Hung, Hao-Ting Wu, Derk O. Verschure, Hein J. Verberne, Chiemi Kitamura
Annals of Nuclear Cardiology.2023; 9(1): 54. CrossRef
Clinical biomarkers for Lewy body diseases
Mai M. Abdelmoaty, Eugene Lu, Rana Kadry, Emma G. Foster, Shaurav Bhattarai, R. Lee Mosley, Howard E. Gendelman
Cell & Bioscience.2023;[Epub] CrossRef
Proteomic comparison between non‐purified cerebrospinal fluid and cerebrospinal fluid‐derived extracellular vesicles from patients with Alzheimer's, Parkinson's and Lewy body dementia
Yael Hirschberg, Natalia Valle‐Tamayo, Oriol Dols‐Icardo, Sebastiaan Engelborghs, Bart Buelens, Roosmarijn E. Vandenbroucke, Yannick Vermeiren, Kurt Boonen, Inge Mertens
Journal of Extracellular Vesicles.2023;[Epub] CrossRef
The connection between cerebral amyloid angiopathy and Alzheimer’s disease
Hans Rolf Jäger
European Radiology.2023; 34(4): 2171. CrossRef
Autonomic symptoms are predictive of dementia with Lewy bodies
Wenzheng Hu, Shuai Liu, Fei Wang, Han Zhu, Xiaoshan Du, Lingyun Ma, Jinghuan Gan, Hao Wu, Xiaodan Wang, Yong Ji
Parkinsonism & Related Disorders.2022; 95: 1. CrossRef
Delusion and Delirium in Neurodegenerative Disorders: An Overlooked Relationship?
Daniele Urso, Valentina Gnoni, Marco Filardi, Giancarlo Logroscino
Frontiers in Psychiatry.2022;[Epub] CrossRef
Clinical Trajectories at the End of Life in Autopsy-Confirmed Dementia Patients With Alzheimer Disease and Lewy Bodies Pathologies
Yian Gu, Anton Kociolek, Kayri K. Fernandez, Stephanie A. Cosentino, Carolyn Wei Zhu, Zhezhen Jin, James B. Leverenz, Yaakov B. Stern
Neurology.2022;[Epub] CrossRef
Diagnostic Performance for Differential Diagnosis of Atypical Parkinsonian Syndromes from Parkinson’s Disease Using Quantitative Indices of 18F-FP-CIT PET/CT
Miju Cheon, Seung Min Kim, Sang-Won Ha, Min Ju Kang, Hea-Eun Yang, Jang Yoo
Diagnostics.2022; 12(6): 1402. CrossRef
The promise of amplification assays for accurate early detection of α-synucleinopathies: A review
Regina Kurapova, Leonidas Chouliaras, John T. O'Brien
Experimental Gerontology.2022; 165: 111842. CrossRef
Progressive Olfactory Impairment and Cardiac Sympathetic Denervation in REM Sleep Behavior Disorder
Annette Janzen, David Vadasz, Jan Booij, Markus Luster, Damiano Librizzi, Martin T. Henrich, Lars Timmermann, Mahboubeh Habibi, Elisabeth Sittig, Geert Mayer, Fanni Geibl, Wolfgang Oertel
Journal of Parkinson's Disease.2022; 12(6): 1921. CrossRef
A Systematic Review and Comparison of Neurocognitive Features of Late-Life Attention-Deficit/Hyperactivity Disorder and Dementia With Lewy Bodies
Jennifer L. Prentice, Morgan J. Schaeffer, Alexandra K. Wall, Brandy L. Callahan
Journal of Geriatric Psychiatry and Neurology.2021; 34(5): 466. CrossRef
Dementia with Lewy bodies in first-generation immigrants in a European memory clinic
Kurt Segers, Florence Benoit, Jean-Marie Meyts, Gérald Glibert, Sophie Levy, Murielle Surquin
Acta Neurologica Belgica.2021; 121(1): 219. CrossRef
The development of new method to differentiate between Dementia with Lewy bodies and Alzheimer’s disease by cerebral perfusion SPECT-comparison to CIScore
Gaku Honda, Shigeki Nagamachi, Masanari Nonokuma, Koichi Takano, Yasuo Kuwabara, Kengo Yoshimitsu, Hitoshi Iida, Koji Ogomori, Hiroaki Kawasaki, Yoshio Tsuboi
Japanese Journal of Radiology.2021; 39(2): 198. CrossRef
Impaired meningeal lymphatic drainage in patients with idiopathic Parkinson’s disease
Xue-Bing Ding, Xin-Xin Wang, Dan-Hao Xia, Han Liu, Hai-Yan Tian, Yu Fu, Yong-Kang Chen, Chi Qin, Jiu-Qi Wang, Zhi Xiang, Zhong-Xian Zhang, Qin-Chen Cao, Wei Wang, Jia-Yi Li, Erxi Wu, Bei-Sha Tang, Ming-Ming Ma, Jun-Fang Teng, Xue-Jing Wang
Nature Medicine.2021; 27(3): 411. CrossRef
Mechanisms of Neurodegeneration in Various Forms of Parkinsonism—Similarities and Differences
Dariusz Koziorowski, Monika Figura, Łukasz M. Milanowski, Stanisław Szlufik, Piotr Alster, Natalia Madetko, Andrzej Friedman
Cells.2021; 10(3): 656. CrossRef
Advances in computerized MRI‐based biomarkers in Alzheimer’s disease
Raymond Wong, Yishan Luo, Vincent Chung-tong Mok, Lin Shi
Brain Science Advances.2021; 7(1): 26. CrossRef
Convolutional neural network-based automatic heart segmentation and quantitation in 123I-metaiodobenzylguanidine SPECT imaging
Shintaro Saito, Kenichi Nakajima, Lars Edenbrandt, Olof Enqvist, Johannes Ulén, Seigo Kinuya
EJNMMI Research.2021;[Epub] CrossRef
A direct comparison of the 2005 and 2017 criteria for dementia with Lewy bodies
Kurt Segers, Florence Benoit, Jean‐Marie Meyts, Gerald Glibert, Murielle Surquin
Psychogeriatrics.2020; 20(5): 785. CrossRef
Calibrated scintigraphic imaging procedures improve quantitative assessment of the cardiac sympathetic nerve activity
Koichi Okuda, Kenichi Nakajima, Chiemi Kitamura, Yumiko Kirihara, Mitsumasa Hashimoto, Seigo Kinuya
Scientific Reports.2020;[Epub] CrossRef

Cerebrospinal Fluid Amyloid β_1-42, Tau, and Alpha-Synuclein Predict the Heterogeneous Progression of Cognitive Dysfunction in Parkinson’s Disease: Ju-Hee Kang; J Mov Disord. 2016;9(2):89-96. Published online May 25, 2016; DOI: https://doi.org/10.14802/jmd.16017

20,057 View
243 Download
18 Web of Science
18 Crossref

Abstract PDF

Parkinson’s disease (PD) is a neurodegenerative disease with heterogeneous pathological and clinical features. Cognitive dysfunction, a frequent non-motor complication, is a risk factor for poor prognosis and shows inter-individual variation in its progression. Of the clinical studies performed to identify biomarkers of PD progression, the Parkinson’s Progression Markers Initiative (PPMI) study is the largest study that enrolled drug-naïve and very early stage PD patients. The baseline characteristics of the PPMI cohort were recently published. The diagnostic utility of cerebrospinal fluid (CSF) biomarkers, including alpha-synuclein (α-syn), total tau, phosphorylated tau at Thr₁₈₁, and amyloid β_1-42, was not satisfactory. However, the baseline data on CSF biomarkers in the PPMI study suggested that the measurement of the CSF biomarkers enables the prediction of future cognitive decline in PD patients, which was consistent with previous studies. To prove the hypothesis that the interaction between Alzheimer’s pathology and α-syn pathology is important to the progression of cognitive dysfunction in PD, longitudinal observational studies must be followed. In this review, the neuropathological nature of heterogeneous cognitive decline in PD is briefly discussed, followed by a summarized interpretation of baseline CSF biomarkers derived from the data in the PPMI study. The combination of clinical, biochemical, genetic and imaging biomarkers of PD constitutes a feasible strategy to predict the heterogeneous progression of PD.

Citations

Citations to this article as recorded by

Highly sensitive biosensor based on IGZO thin-film transistors for detection of Parkinson's disease
Tongzheng Li, Tongying Xu, Zhengyang Yao, Yanan Ding, Guoxia Liu, Fukai Shan
Applied Physics Letters.2023;[Epub] CrossRef
Extracellular vesicle biomarkers for cognitive impairment in Parkinson’s disease
Joseph Blommer, Toni Pitcher, Maja Mustapic, Erden Eren, Pamela J Yao, Michael P Vreones, Krishna A Pucha, John Dalrymple-Alford, Reza Shoorangiz, Wassilios G Meissner, Tim Anderson, Dimitrios Kapogiannis
Brain.2023; 146(1): 195. CrossRef
Imaging Biomarkers for Central Nervous System Drug Development and Future Clinical Utility: Lessons from Neurodegenerative Disorders
John P. Seibyl
Journal of Nuclear Medicine.2023; 64(1): 12. CrossRef
REM sleep behavior disorder and cerebrospinal fluid alpha-synuclein, amyloid beta, total tau and phosphorylated tau in Parkinson’s disease: a cross-sectional and longitudinal study
Fardin Nabizadeh, Kasra Pirahesh, Parya Valizadeh
Journal of Neurology.2022; 269(9): 4836. CrossRef
Longitudinal Analysis of Multiple Neurotransmitter Metabolites in Cerebrospinal Fluid in Early Parkinson's Disease
Thomas Kremer, Kirsten I. Taylor, Juliane Siebourg‐Polster, Thomas Gerken, Andreas Staempfli, Christian Czech, Juergen Dukart, Douglas Galasko, Tatiana Foroud, Lana M. Chahine, Christopher S. Coffey, Tanya Simuni, Daniel Weintraub, John Seibyl, Kathleen L
Movement Disorders.2021; 36(8): 1972. CrossRef
Cerebrospinal fluid biomarkers in Parkinson’s disease with freezing of gait: an exploratory analysis
J. M. Hatcher-Martin, J. L. McKay, A. F. Pybus, B. Sommerfeld, J. C. Howell, F. C. Goldstein, L. Wood, W. T. Hu, S. A. Factor
npj Parkinson's Disease.2021;[Epub] CrossRef
Melatonin affects the release of exosomes and tau-content in in vitro amyloid-beta toxicity model
Mehmet Ozansoy, Muzaffer Beyza Ozansoy, Burak Yulug, Seyda Cankaya, Ertugrul Kilic, Sule Goktekin, Ulkan Kilic
Journal of Clinical Neuroscience.2020; 73: 237. CrossRef
Disentangling the Amyloid Pathways: A Mechanistic Approach to Etiology
Maja Malmberg, Tarja Malm, Oskar Gustafsson, Andrea Sturchio, Caroline Graff, Alberto J. Espay, Anthony P. Wright, Samir El Andaloussi, Anders Lindén, Kariem Ezzat
Frontiers in Neuroscience.2020;[Epub] CrossRef
Why would Parkinson’s disease lead to sudden changes in creativity, motivation, or style with visual art?: A review of case evidence and new neurobiological, contextual, and genetic hypotheses
Jon O. Lauring, Tomohiro Ishizu, Hana H. Kutlikova, Felix Dörflinger, Steven Haugbøl, Helmut Leder, Ron Kupers, Matthew Pelowski
Neuroscience & Biobehavioral Reviews.2019; 100: 129. CrossRef
Beta Amyloid Deposition Is Not Associated With Cognitive Impairment in Parkinson's Disease
Tracy R. Melzer, Megan R. Stark, Ross J. Keenan, Daniel J. Myall, Michael R. MacAskill, Toni L. Pitcher, Leslie Livingston, Sophie Grenfell, Kyla-Louise Horne, Bob N. Young, Maddie J. Pascoe, Mustafa M. Almuqbel, Jian Wang, Steven H. Marsh, David H. Mille
Frontiers in Neurology.2019;[Epub] CrossRef
Dementia with Lewy bodies and Parkinson’s disease-dementia: current concepts and controversies
Kurt A. Jellinger
Journal of Neural Transmission.2018; 125(4): 615. CrossRef
Identification of a prospective early motor progression cluster of Parkinson's disease: Data from the PPMI study
George D. Vavougios, Triantafyllos Doskas, Constantinos Kormas, Karen A. Krogfelt, Sotirios G. Zarogiannis, Leonidas Stefanis
Journal of the Neurological Sciences.2018; 387: 103. CrossRef
Relationship between cerebrospinal fluid biomarkers and structural brain network properties in Parkinson's disease
Nooshin Abbasi, Bahram Mohajer, Sima Abbasi, Payam Hasanabadi, Amirhussein Abdolalizadeh, Reza Rajimehr
Movement Disorders.2018; 33(3): 431. CrossRef
Longitudinal Alterations of Alpha-Synuclein, Amyloid Beta, Total, and Phosphorylated Tau in Cerebrospinal Fluid and Correlations Between Their Changes in Parkinson's Disease
Mahsa Dolatshahi, Shayan Pourmirbabaei, Aida Kamalian, Amir Ashraf-Ganjouei, Mehdi Yaseri, Mohammad H. Aarabi
Frontiers in Neurology.2018;[Epub] CrossRef
Ratios of proteins in cerebrospinal fluid in Parkinson's disease cognitive decline: prospective study
Manuel Delgado‐Alvarado, Rosalía Dacosta‐Aguayo, Irene Navalpotro‐Gómez, Belén Gago, Ana Gorostidi, Haritz Jiménez‐Urbieta, Ana Quiroga‐Varela, Javier Ruiz‐Martínez, Alberto Bergareche, María C. Rodríguez‐Oroz
Movement Disorders.2018; 33(11): 1809. CrossRef
Extracellular Vesicles as a Source of Urological Biomarkers: Lessons Learned From Advances and Challenges in Clinical Applications to Major Diseases
Ji-Young Choi, Sujin Kim, Hyo-Bum Kwak, Dong-Ho Park, Jae-Hyoung Park, Jeong-Seon Ryu, Chang-Shin Park, Ju-Hee Kang
International Neurourology Journal.2017; 21(2): 83. CrossRef
Candidate inflammatory biomarkers display unique relationships with alpha-synuclein and correlate with measures of disease severity in subjects with Parkinson’s disease
Lori N. Eidson, George T. Kannarkat, Christopher J. Barnum, Jianjun Chang, Jaegwon Chung, Chelsea Caspell-Garcia, Peggy Taylor, Brit Mollenhauer, Michael G. Schlossmacher, Larry Ereshefsky, Mark Yen, Catherine Kopil, Mark Frasier, Kenneth Marek, Vicki S.
Journal of Neuroinflammation.2017;[Epub] CrossRef
Cognitive and Neuropsychiatric Features in Parkinson's and Lewy Body Dementias
Julie A Fields
Archives of Clinical Neuropsychology.2017; 32(7): 786. CrossRef

Mechanism of Anti-α-Synuclein Immunotherapy: Jun Sung Lee, Seung-Jae Lee; J Mov Disord. 2016;9(1):14-19. Published online January 25, 2016; DOI: https://doi.org/10.14802/jmd.15059

25,517 View
332 Download
35 Web of Science
35 Crossref

Abstract PDF

Immunization therapy targeting α-synuclein has emerged as a promising approach for Parkinson’s disease and perhaps for other synucleinopathies. Several antibodies have shown therapeutic effects in mouse models of synucleinopathies and have alleviated the pathological and behavioral phenotypes of these mice. The mechanisms through which the immunization therapy works were initially puzzling, especially given that α-synuclein is a typical cytosolic protein. Recent studies, however, suggested that extracellular α-synuclein is an important pathogenic entity, and hence, a target for immunotherapy. Here, we review the literature describing immunization therapy for synucleinopathies in mouse models and provide current thoughts on the potential mechanisms underlying the therapeutic effects of α-synuclein immunotherapy.

Citations

Citations to this article as recorded by

Aggregation-Induced Emission Luminogens: A New Possibility for Efficient Visualization of RNA in Plants
Zheng-Chao Yang, Li-Xiang Zhao, Yu-Qi Sang, Xin Huang, Xuan-Chen Lin, Zhi-Ming Yu
Plants.2024; 13(5): 743. CrossRef
Immunisation with UB-312 in the Thy1SNCA mouse prevents motor performance deficits and oligomeric α-synuclein accumulation in the brain and gut
Jacqui T. Nimmo, Harry Smith, Chang Yi Wang, Jessica L. Teeling, James A. R. Nicoll, Ajay Verma, Jean-Cosme Dodart, Zhi Liu, Feng Lin, Roxana O. Carare
Acta Neuropathologica.2022; 143(1): 55. CrossRef
Autophagy-Related Pathways in Vesicular Unconventional Protein Secretion
Shin Hye Noh, Ye Jin Kim, Min Goo Lee
Frontiers in Cell and Developmental Biology.2022;[Epub] CrossRef
Targeting Macroautophagy as a Therapeutic Opportunity to Treat Parkinson’s Disease
Irene Sanchez-Mirasierra, Saurav Ghimire, Sergio Hernandez-Diaz, Sandra-Fausia Soukup
Frontiers in Cell and Developmental Biology.2022;[Epub] CrossRef
A quantitative systems pharmacology model for simulating OFF-Time in augmentation trials for Parkinson’s disease: application to preladenant
Rachel Rose, Emma Mitchell, Piet Van Der Graaf, Daisuke Takaichi, Jun Hosogi, Hugo Geerts
Journal of Pharmacokinetics and Pharmacodynamics.2022; 49(6): 593. CrossRef
Neuroimmune crosstalk and evolving pharmacotherapies in neurodegenerative diseases
Falguni Baidya, Mariya Bohra, Aishika Datta, Deepaneeta Sarmah, Birva Shah, Priya Jagtap, Swapnil Raut, Ankan Sarkar, Upasna Singh, Kiran Kalia, Anupom Borah, Xin Wang, Kunjan R. Dave, Dileep R. Yavagal, Pallab Bhattacharya
Immunology.2021; 162(2): 160. CrossRef
Electrogastrography for diagnosis of early-stage Parkinson's disease
Nobuyuki Araki, Yoshitaka Yamanaka, Anupama Poudel, Yoshikatsu Fujinuma, Akira Katagiri, Satoshi Kuwabara, Masato Asahina
Parkinsonism & Related Disorders.2021; 86: 61. CrossRef
Natural Alkaloid Compounds as Inhibitors for Alpha-Synuclein Seeded Fibril Formation and Toxicity
Simona S. Ghanem, Hend S. Fayed, Qi Zhu, Jia-Hong Lu, Nishant N. Vaikath, Janarthanan Ponraj, Said Mansour, Omar M. A. El-Agnaf
Molecules.2021; 26(12): 3736. CrossRef
Tat-p27 Ameliorates Neuronal Damage Reducing α-Synuclein and Inflammatory Responses in Motor Neurons After Spinal Cord Ischemia
Woosuk Kim, Hyun Jung Kwon, Hyo Young Jung, Kyu Ri Hahn, Seung Myung Moon, Yeo Sung Yoon, In Koo Hwang, Soo Young Choi, Dae Won Kim
Neurochemical Research.2021; 46(12): 3123. CrossRef
Immunotherapies for Parkinson’s Disease: Progression of Clinical Development
Jet Shee Teng, Yin Yin Ooi, Soi Moi Chye, Anna Pick Kiong Ling, Rhun Yian Koh
CNS & Neurological Disorders - Drug Targets.2021; 20(9): 802. CrossRef
Parkinson Disease: Translating Insights from Molecular Mechanisms to Neuroprotection
Sheila K. Pirooznia, Liana S. Rosenthal, Valina L. Dawson, Ted M. Dawson, Eric Barker
Pharmacological Reviews.2021; 73(4): 1204. CrossRef
Anti-inflammatory and Neuroprotective Agents in Clinical Trials for CNS Disease and Injury: Where Do We Go From Here?
Khalil Mallah, Christine Couch, Davis M. Borucki, Amer Toutonji, Mohammed Alshareef, Stephen Tomlinson
Frontiers in Immunology.2020;[Epub] CrossRef
Targeting α-synuclein by PD03 AFFITOPE® and Anle138b rescues neurodegenerative pathology in a model of multiple system atrophy: clinical relevance
Miguel Lemos, Serena Venezia, Violetta Refolo, Antonio Heras-Garvin, Sabine Schmidhuber, Armin Giese, Andrei Leonov, Sergey Ryazanov, Christian Griesinger, Gergana Galabova, Guenther Staffler, Gregor Karl Wenning, Nadia Stefanova
Translational Neurodegeneration.2020;[Epub] CrossRef
Insights Into Peptide Inhibition of Alpha-Synuclein Aggregation
James H. Torpey, Richard M. Meade, Ravina Mistry, Jody M. Mason, Jillian Madine
Frontiers in Neuroscience.2020;[Epub] CrossRef
Novel antibodies detect additional α-synuclein pathology in synucleinopathies: potential development for immunotherapy
Jacqui T. Nimmo, Ajay Verma, Jean-Cosme Dodart, Chang Yi Wang, Jimmy Savistchenko, Ronald Melki, Roxana O. Carare, James A. R. Nicoll
Alzheimer's Research & Therapy.2020;[Epub] CrossRef
Cellular and Molecular Aspects of Parkinson Treatment: Future Therapeutic Perspectives
Khosro Jamebozorgi, Eskandar Taghizadeh, Daryoush Rostami, Hosein Pormasoumi, George E. Barreto, Seyed Mohammad Gheibi Hayat, Amirhossein Sahebkar
Molecular Neurobiology.2019; 56(7): 4799. CrossRef
The Associations between Immunological Reactivity to the Haptenation of Unconjugated Bisphenol A to Albumin and Protein Disulfide Isomerase with Alpha-Synuclein Antibodies
Datis Kharrazian, Martha Herbert, Aristo Vojdani
Toxics.2019; 7(2): 26. CrossRef
Effects of single and combined immunotherapy approach targeting amyloid β protein and α‐synuclein in a dementia with Lewy bodies–like model
Markus Mandler, Edward Rockenstein, Cassia Overk, Michael Mante, Jazmin Florio, Anthony Adame, Changyoun Kim, Radmila Santic, Achim Schneeberger, Frank Mattner, Sabine Schmidhuber, Gergana Galabova, Brian Spencer, Eliezer Masliah, Robert A. Rissman
Alzheimer's & Dementia.2019; 15(9): 1133. CrossRef
Translational therapies for multiple system atrophy: Bottlenecks and future directions
Nadia Stefanova
Autonomic Neuroscience.2018; 211: 7. CrossRef
Integrin CD11b mediates α-synuclein-induced activation of NADPH oxidase through a Rho-dependent pathway
Liyan Hou, Xiuqi Bao, Caixia Zang, Hanyu Yang, Fuqiang Sun, Yuning Che, Xuefei Wu, Shao Li, Dan Zhang, Qingshan Wang
Redox Biology.2018; 14: 600. CrossRef
Serum titers of autoantibodies against α-synuclein and tau in child- and adulthood
Isabell Kuhn, Tobias Rogosch, Theresa I. Schindler, Björn Tackenberg, Michael Zemlin, Rolf F. Maier, Richard Dodel, Yannick Kronimus
Journal of Neuroimmunology.2018; 315: 33. CrossRef
Beneficial Effects of Flavonoids Against Parkinson's Disease
Un Ju Jung, Sang Ryong Kim
Journal of Medicinal Food.2018; 21(5): 421. CrossRef
Unconventional protein secretion – new insights into the pathogenesis and therapeutic targets of human diseases
Jiyoon Kim, Heon Yung Gee, Min Goo Lee
Journal of Cell Science.2018;[Epub] CrossRef
Region-Specific Effects of Immunotherapy With Antibodies Targeting α-synuclein in a Transgenic Model of Synucleinopathy
Martin Kallab, Marcos Herrera-Vaquero, Malin Johannesson, Fredrik Eriksson, Jessica Sigvardson, Werner Poewe, Gregor K. Wenning, Eva Nordström, Nadia Stefanova
Frontiers in Neuroscience.2018;[Epub] CrossRef
Gene therapy for neurological disorders: progress and prospects
Benjamin E. Deverman, Bernard M. Ravina, Krystof S. Bankiewicz, Steven M. Paul, Dinah W. Y. Sah
Nature Reviews Drug Discovery.2018; 17(9): 641. CrossRef
Combined Active Humoral and Cellular Immunization Approaches for the Treatment of Synucleinopathies
Edward Rockenstein, Gary Ostroff, Fusun Dikengil, Florentina Rus, Michael Mante, Jazmin Florio, Anthony Adame, Ivy Trinh, Changyoun Kim, Cassia Overk, Eliezer Masliah, Robert A. Rissman
The Journal of Neuroscience.2018; 38(4): 1000. CrossRef
Holocranohistochemistry enables the visualization of α-synuclein expression in the murine olfactory system and discovery of its systemic anti-microbial effects
Julianna J. Tomlinson, Bojan Shutinoski, Li Dong, Fanyi Meng, Dina Elleithy, Nathalie A. Lengacher, Angela P. Nguyen, Greg O. Cron, Qiubo Jiang, Erik D. Roberson, Robert L. Nussbaum, Nour K. Majbour, Omar M. El-Agnaf, Steffany A. Bennett, Diane C. Lagace,
Journal of Neural Transmission.2017; 124(6): 721. CrossRef
Structure, Distribution, and Genetic Profile of α-Synuclein and Their Potential Clinical Application in Parkinson’s Disease
Xiaoli Si, Jiali Pu, Baorong Zhang
Journal of Movement Disorders.2017; 10(2): 69. CrossRef
Membrane Trafficking Illuminates a Path to Parkinson’s Disease
Takafumi Hasegawa, Naoto Sugeno, Akio Kikuchi, Toru Baba, Masashi Aoki
The Tohoku Journal of Experimental Medicine.2017; 242(1): 63. CrossRef
Decelerated neurodegeneration after intravitreal injection of α-synuclein antibodies in a glaucoma animal model
J. Teister, F. Anders, S. Beck, S. Funke, H. von Pein, V. Prokosch, N. Pfeiffer, F. Grus
Scientific Reports.2017;[Epub] CrossRef
Impact of aging immune system on neurodegeneration and potential immunotherapies
Zhanfeng Liang, Yang Zhao, Linhui Ruan, Linnan Zhu, Kunlin Jin, Qichuan Zhuge, Dong-Ming Su, Yong Zhao
Progress in Neurobiology.2017; 157: 2. CrossRef
A novel panel of α-synuclein antibodies reveal distinctive staining profiles in synucleinopathies
Jess-Karan S. Dhillon, Cara Riffe, Brenda D. Moore, Yong Ran, Paramita Chakrabarty, Todd E. Golde, Benoit I. Giasson, Stephan N. Witt
PLOS ONE.2017; 12(9): e0184731. CrossRef
Vaccination strategies in tauopathies and synucleinopathies
Anne K. Braczynski, Jörg B. Schulz, Jan‐Philipp Bach
Journal of Neurochemistry.2017; 143(5): 467. CrossRef
Missions of <italic>Journal of Movement Disorders</italic>
Yun Joong Kim
Journal of Movement Disorders.2016; 9(1): 1. CrossRef
How strong is the evidence that Parkinson's disease is a prion disorder?
Patrik Brundin, Jiyan Ma, Jeffrey H. Kordower
Current Opinion in Neurology.2016; 29(4): 459. CrossRef

First
Prev
Page of 1
Next
Last

Search