Article
Biochemistry & Molecular Biology
Jonas Folke, Emil Bergholt, Bente Pakkenberg, Susana Aznar, Tomasz Brudek
Summary: This study investigates the autoimmune aberrancies towards alpha-synuclein in prodromal phases of multiple-system trophy and Parkinson's Disease. The results indicate impaired reactivity towards alpha-synuclein occurs before disease onset, which may result in reduced clearance and aggregation of the protein.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Xiao-Tong Wang, Huan Yu, Feng-Tao Liu, Can Zhang, Ya-Hui Ma, Jian Wang, Qiang Dong, Lan Tan, Han Wang, Jin-Tai Yu
Summary: The study found that sleep disorders were associated with decreased levels of CSF alpha-syn, which may be important for monitoring disease progression and preventing the spread of alpha-syn pathology.
JOURNAL OF NEUROLOGY
(2022)
Editorial Material
Clinical Neurology
Sandrina Weber, Brit Mollenhauer
Summary: Predicting the conversion from isolated REM sleep behavior disorder to Parkinson disease is crucial, and a new study suggests that detecting misfolded alpha-synuclein in cerebrospinal fluid is a good marker of conversion risk. However, the inability to predict the timeline of progression may limit its utility.
NATURE REVIEWS NEUROLOGY
(2021)
Article
Neurosciences
Liza Bergkvist, Michaela E. Johnson, Gabriela Mercado, Jennifer A. Steiner, Lindsay Meyerdirk, Emily Schulz, Zachary Madaj, Jiyan Ma, Katelyn Becker, Yazhou Li, Patrik Brundin
Summary: Repurposing of drugs intended for type 2 diabetes treatment to address Parkinson's disease has shown potential, especially with the use of GLP-1 analogues. However, the results of these treatments can vary significantly depending on the nature of neuronal damage and the specific neuronal population being targeted.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Medicine, General & Internal
G. Pagano, K. I. Taylor, J. Anzures-Cabrera, M. Marchesi, T. Simuni, K. Marek, R. B. Postuma, N. Pavese, F. Stocchi, J. -P. Azulay, B. Mollenhauer, L. Lopez-Manzanares, D. S. Russell, J. T. Boyd, A. P. Nicholas, M. R. Luquin, R. A. Hauser, T. Gasser, W. Poewe, B. Ricci, A. Boulay, A. Vogt, F. G. Boess, J. Dukart, G. D'Urso, R. Finch, S. Zanigni, A. Monnet, N. Pross, A. Hahn, H. Svoboda, M. Britschgi, F. Lipsmeier, E. Volkova-Volkmar, M. Lindemann, S. Dziadek, S. Holiga, D. Rukina, T. Kustermann, G. A. Kerchner, P. Fontoura, D. Umbricht, R. Doody, T. Nikolcheva, A. Bonni
Summary: The study found that prasinezumab had no meaningful effect on global or imaging measures of Parkinson's disease progression and was associated with infusion reactions.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Review
Neurosciences
Thomas Koeglsperger, Svenja-Lotta Rumpf, Patricia Schliesser, Felix L. Struebing, Matthias Brendel, Johannes Levin, Claudia Trenkwalder, Guenter U. Hoeglinger, Jochen Herms
Summary: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons. Previous studies have identified cellular and molecular changes that occur before the appearance of Lewy bodies (LBs) in these neurons. Understanding these early pathological events may help in the development of therapeutic and diagnostic strategies for PD.
MOLECULAR NEURODEGENERATION
(2023)
Article
Biochemistry & Molecular Biology
Chen-Chih Chung, Lung Chan, Jia-Hung Chen, Yi-Chieh Hung, Chien-Tai Hong
Summary: Plasma extracellular vesicle (EV) alpha-synuclein levels were significantly lower in patients with Parkinson's disease (PD) compared to controls, and were associated with the severity of akinetic-rigidity symptoms in PD patients. This study supports the diagnostic potential and clinical relevance of plasma EV alpha-synuclein as a biomarker for PD subtyping.
Review
Biochemistry & Molecular Biology
Abbie T. Rodger, Maryam A. L. Nasser, Wayne G. Carter
Summary: Currently, there are no pharmacological treatments that can completely stop or reverse the progression of Parkinson's Disease (PD). Therefore, there is a need for neuroprotective therapies. This systematic review examines the effectiveness of anti-a-synuclein (a-syn) therapies in preventing PD progression in preclinical models and human clinical trials. The review found that novel preclinical anti-a-syn therapeutics reduced a-syn aggregations and protected against dopaminergic neuronal loss. Completed clinical trials showed significant tolerability and efficacy in reducing a-syn and minimal adverse effects. Overall, this review highlights the potential of anti-a-syn therapies in both preclinical and clinical settings to reduce a-syn accumulation and potentially slow down PD progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Masashi Ikuno, Hodaka Yamakado, Ikuko Amano, Yusuke Hatanaka, Norihito Uemura, Shu-ichi Matsuzawa, Ryosuke Takahashi
Summary: Metabolomic analysis of plasma from a mouse model of prodromal Parkinson's disease (p-PD) revealed abnormalities in mitochondrial beta-oxidation and dysfunction, potentially serving as early biomarkers for PD.
NEUROSCIENCE LETTERS
(2021)
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)
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)
Review
Neurosciences
Miriam Hojholt Terkelsen, Ida H. Klaestrup, Victor Hvingelby, Johanne Lauritsen, Nicola Pavese, Marina Romero-Ramos
Summary: This paper reviews the evidence of neuroinflammation and peripheral immune changes in Parkinson's disease, discusses their pathological roles, and considers factors associated with the immune response.
JOURNAL OF PARKINSONS DISEASE
(2022)
Article
Neurosciences
S. Hayley, F. Vahid-Ansari, H. Sun, P. R. Albert
Summary: Parkinson's disease is a complex illness influenced by environmental factors and genetic vulnerability. Many studies focus on the disease's motor symptoms and overlook the debilitating non-motor features that occur early in the disease process. Comorbid psychiatric features, such as clinical depression, anxiety, and sleep disorders, are believed to emerge before prominent motor deficits. This review explores the prodromal stage of PD, the unfolding of early neuropsychiatric pathology, and later motor disturbances, as well as the complexity captured by animal models of PD.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Clinical Neurology
Sonia Monge-Garcia, Maria-Salud Garcia-Ayllon, Jose Sanchez-Paya, Ruth Gasparini-Berenguer, Maria-Angeles Cortes-Gomez, Javier Saez-Valero, Jose-Antonio Monge-Argiles
Summary: This study evaluated the diagnostic validity of alpha-synuclein (AS) levels in the cerebrospinal fluid (CSF) as a predictor of psychotic symptoms (PS) in patients with mild cognitive impairment. The results showed that AS levels were able to differentiate between the psychotic and non-psychotic groups, achieving at least 80% sensitivity.
FRONTIERS IN NEUROLOGY
(2023)
Article
Geriatrics & Gerontology
Kyu Hwan Shim, Han Gyeol Go, Heewon Bae, Da-Eun Jeong, Danyeong Kim, Young Chul Youn, SangYun Kim, Seong Soo A. An, Min Ju Kang
Summary: Exosomal AChE activity is significantly decreased in PD patients compared to healthy controls, and shows a strong negative correlation with disease severity. This implies its potential as a reliable biomarker for early diagnosis and prognosis of PD.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Oncology
Carolina A. Parada, Joshua W. Osbun, Tina Busald, Yigit Karasozen, Sumanpreet Kaur, Min Shi, Jason Barber, Widya Adidharma, Patrick J. Cimino, Catherine Pan, Luis F. Gonzalez-Cuyar, Robert Rostomily, Donald E. Born, Jing Zhang, Manuel Ferreira
CLINICAL CANCER RESEARCH
(2020)
Article
Radiology, Nuclear Medicine & Medical Imaging
Santiago Bullich, Olivier Barret, Cristian Constantinescu, Christine Sandiego, Andre Mueller, Mathias Berndt, Caroline Papin, Audrey Perrotin, Norman Koglin, Heiko Kroth, Andrea Pfeifer, Gilles Tamagnan, Jennifer Madonia, John P. Seibyl, Kenneth Marek, Susan De Santi, Ludger M. Dinkelborg, Andrew W. Stephens
JOURNAL OF NUCLEAR MEDICINE
(2020)
Article
Radiology, Nuclear Medicine & Medical Imaging
Andre Mueller, Santiago Bullich, Olivier Barret, Jennifer Madonia, Mathias Berndt, Caroline Papin, Audrey Perrotin, Norman Koglin, Heiko Kroth, Andrea Pfeifer, Gilles D. Tamagnan, John P. Seibyl, Kenneth Marek, Susan De Santi, Ludger M. Dinkelborg, Andrew W. Stephens
JOURNAL OF NUCLEAR MEDICINE
(2020)
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
Tanya Simuni, Michael C. Brumm, Liz Uribe, Chelsea Caspell-Garcia, Christopher S. Coffey, Andrew Siderowf, Roy Alcalay, John Q. Trojanowski, Leslie M. Shaw, John Seibyl, Andrew Singleton, Arthur W. Toga, Doug Galasko, Tatiana Foroud, Kelly Nudelman, Duygu Tosun-Turgut, Kathleen Poston, Daniel Weintraub, Brit Mollenhauer, Caroline M. Tanner, Karl Kieburtz, Lana M. Chahine, Alyssa Reimer, Samantha Hutten, Susan Bressman, Kenneth Marek, Christopher Coffey, Caroline Tanner, Arthur Toga, Douglas Galasko, Werner Poewe, Vanessa Arnedo, Adrienne Clark, Mark Frasier, Catherine Kopil, Sohini Chowdhury, Todd Sherer, Nichole Daegele, Cynthia Casaceli, Ray Dorsey, Renee Wilson, Sugi Mahes, Christina Salerno, Karen Crawford, Paola Casalin, Giulia Malferrari, Mali Gani Weisz, Avi Orr-Urtreger, John Trojanowski, Leslie Shaw, 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, 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, Lisbeth Carvajal, 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
MOVEMENT DISORDERS
(2020)
Article
Neurosciences
Lana M. Chahine, Iris Chin, Chelsea Caspell-Garcia, David G. Standaert, Ethan Brown, Luba Smolensky, Vanessa Arnedo, Daisy Daeschler, Lindsey Riley, Monica Korell, Roseanne Dobkin, Ninad Amondikar, Stephen Gradinscak, Ira Shoulson, Marissa Dean, Kevin Kwok, Paul Cannon, Kenneth Marek, Catherine Kopil, Caroline M. Tanner, Connie Marras
JOURNAL OF PARKINSONS DISEASE
(2020)
Article
Clinical Neurology
Lana M. Chahine, Michael C. Brumm, Chelsea Caspell-Garcia, Wolfgang Oertel, Brit Mollenhauer, Amy Amara, Ana Fernandez-Arcos, Eduardo Tolosa, Cristina Simonet, Birgit Hogl, Aleksandar Videnovic, Samantha J. Hutten, Caroline Tanner, Daniel Weintraub, Elliot Burghardt, Christopher Coffey, Hyunkeun R. Cho, Karl Kieburtz, Kathleen L. Poston, Kalpana Merchant, Douglas Galasko, Tatiana Foroud, Andrew Siderowf, Kenneth Marek, Tanya Simuni, Alex Iranzo
Summary: The study investigated the utility of DAT imaging as a biomarker for predicting clinically-defined aSN diagnosis in iRBD patients, finding that those with lower than expected baseline DAT binding ratios had a higher risk of aSN diagnosis. The results highlight the potential of DAT imaging in identifying high-risk individuals.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2021)
Article
Neurosciences
Nelson Ferreira, Nadia Pereira Goncalves, Asad Jan, Nanna Moller Jensen, Amelia van der Laan, Simin Mohseni, Christian Bjerggaard Vaegter, Poul Henning Jensen
Summary: This study revealed that inoculation of mouse alpha-synuclein pre-formed fibrils can induce retrograde trans-synaptic spreading of alpha-Syn pathology across sensory neurons and dorsal nerve roots in a transgenic mouse model of PD, leading to impaired nociceptive response, reduced nerve conduction velocities, and fiber degeneration. This suggests a link between the transneuronal propagation of alpha-Syn pathology with sensory neuron dysfunction and neuropathic impairment, providing promising avenues for investigating mechanisms underlying pain in PD.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Neurosciences
Xiaodan Liu, Qilong Wang, Ying Yang, Tessandra Stewart, Min Shi, David Soltys, Genliang Liu, Eric Thorland, Eugene M. Cilento, Yiran Hou, Zongran Liu, Tao Feng, Jing Zhang
Summary: Peripheral biomarkers like reduced CHCHD2 mRNA in erythrocytes can serve as indicators for early detection of Parkinson's disease. Validation studies in brains of PD patients and animal models with alpha-synuclein overexpression confirmed the reduction of CHCHD2, both in protein and mRNA expression. Cell models also demonstrated that overexpression of alpha-synuclein leads to reduced CHCHD2 through altered subcellular localization of p300 histone acetyltransferase. Furthermore, a larger cohort study showed that reduced CHCHD2 mRNA can be utilized as a biomarker for detecting PD, even in early stages, with high sensitivity and specificity.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Laura M. Vecchio, Patricia Sullivan, Amy R. Dunn, Marie Kristel Bermejo, Rong Fu, Shababa T. Masoud, Emil Gregersen, Nikhil M. Urs, Reza Nazari, Poul Henning Jensen, Amy Ramsey, David S. Goldstein, Gary W. Miller, Ali Salahpour
Summary: TH plays a crucial role in Parkinson's disease, increasing TH activity leads to oxidative stress and accumulation of toxic dopamine metabolites in vivo, augmenting toxicity.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Immunology
Emil Gregersen, Cristine Betzer, Woojin S. Kim, Gergo Kovacs, Lasse Reimer, Glenda M. Halliday, Steffen Thiel, Poul Henning Jensen
Summary: The study demonstrates that alpha-synuclein can activate the classical complement pathway, leading to complement-dependent cellular toxicity, which can be rescued by complement inhibitors. There is also a trend for higher levels of C1q in the putamen of MSA patients, suggesting the involvement of the complement system in synucleinopathies.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Clinical Neurology
Chen Tian, Tessandra Stewart, Zhen Hong, Zhen Guo, Patrick Aro, David Soltys, Catherine Pan, Elaine R. Peskind, Cyrus P. Zabetian, Leslie M. Shaw, Douglas Galasko, Joseph F. Quinn, Min Shi, Jing Zhang
Summary: This study identified NMDAR2A, a protein related to synaptic function, as a novel marker of central nervous system-derived plasma extracellular vesicles (EVs) and developed a flow cytometry-based technology to detect these plasma EVs. The assay was tested in patients with Alzheimer's disease (AD) and the results showed significantly reduced CNS-derived EVs in plasma compared to healthy controls. The study demonstrated that analyzing individual neuron-derived synaptic function-related EVs in peripheral blood can serve as a helpful marker for synaptic dysfunction in AD and dementia.
ALZHEIMERS & DEMENTIA
(2023)
Article
Cell Biology
Louise Berkhoudt Lassen, Maj Schneider Thomsen, Elisa Basso, Ernst-Martin Fuchtbauer, Annette Fuchtbauer, Tiago Fleming Outeiro, Poul Henning Jensen, Torben Moos
Summary: Mutations of tyrosine to phenylalanine at positions 125, 133, and 136 in alpha-synuclein lead to severe motor impairment and neuropathology in mice. The phosphorylation of serine 129 does not seem to be the cause of the toxicity.
Article
Clinical Neurology
Zhen Hong, Chen Tian, Tessandra Stewart, Patrick Aro, David Soltys, Matt Bercow, Lifu Sheng, Kayla Borden, Tarek Khrisat, Catherine Pan, Cyrus P. Zabetian, Elaine R. Peskind, Joseph F. Quinn, Thomas J. Montine, Jan Aasly, Min Shi, Jing Zhang
Summary: This study developed a reliable and fast assay to quantify alpha-syn-containing EVs in CSF for Parkinson disease diagnosis, using nanoscale flow cytometry technology. The results showed that total alpha-syn-positive and aggregated alpha-syn-positive EVs in CSF may serve as a helpful tool in PD diagnosis, with a diagnostic accuracy that reached clinical relevance.
Article
Medicine, Research & Experimental
Yaqiong Dong, Tessandra Stewart, Lidan Bai, Xue Li, Ting Xu, Jeffrey Iliff, Min Shi, Danfeng Zheng, Lan Yuan, Taotao Wei, Xiaoda Yang, Jing Zhang
