Article
Clinical Neurology
David J. Koss, Odeta Bondarevaite, Sara Adams, Marta Leite, Flaviano Giorgini, Johannes Attems, Tiago F. Outeiro
Summary: The study found that the reduction of RAB39B in DLB cases is associated with an increase in aSyn and Aβ, potentially leading to aggregation of LBs and synaptic impairment. While total RAB39B levels remained unchanged, the decrease in cytoplasmic pool suggests impaired function. RAB39B may be considered as a future therapeutic target for DLB.
Review
Clinical Neurology
Jon B. Toledo, Carla Abdelnour, Rimona S. Weil, Daniel Ferreira, Federico Rodriguez-Porcel, Andrea Pilotto, Kathryn A. Wyman-Chick, Michel J. Grothe, Joseph P. M. Kane, Angela Taylor, Arvid Rongve, Sonja Scholz, James B. Leverenz, Bradley F. Boeve, Dag Aarsland, Ian G. McKeith, Simon Lewis, Iracema Leroi, John P. Taylor
Summary: Dementia with Le bodies (DLB) is clinically characterized by visual hallucinations, fluctuations, rapid eye movement (REM) sleep behavioral disorder, and parkinsonism. However, neuropathological studies have shown the coexistence of Alzheimer's disease, TAR DNA-binding protein 43 (TDP-43), and cerebrovascular pathologies in DLB cases. These co-pathologies should be taken into consideration in clinical trials for DLB individuals.
ALZHEIMERS & DEMENTIA
(2023)
Review
Neurosciences
Jay Amin, Daniel Erskine, Paul C. Donaghy, Ajenthan Surendranathan, Peter Swann, Amy P. Kunicki, Delphine Boche, Clive Holmes, Ian G. McKeith, John T. O'Brien, Jessica L. Teeling, Alan J. Thomas
Summary: This article provides a review of the role of inflammation in Dementia with Lewy bodies (DLB). The research suggests an increase in cerebral and peripheral inflammation in the early stages of DLB, which decreases as the disease progresses. Alpha-synuclein is found to directly promote inflammation, and the presence of Alzheimer's disease (AD) co-pathology contributes to the profile of neuroinflammation in DLB. Further longitudinal studies are recommended to enhance our understanding of the disease's pathogenesis and develop a composite biomarker for DLB diagnosis and identification of new therapeutic targets.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Neurosciences
David J. Koss, Daniel Erskine, Andrew Porter, Pawel Palmoski, Hariharan Menon, Olivia G. J. Todd, Marta Leite, Johannes Attems, Tiago F. Outeiro
Summary: Through a multidisciplinary approach, this study confirms the presence of nuclear alpha-synuclein in the brains of patients with dementia with Lewy bodies, which may undergo pathogenic modifications and contribute to the disease phenotype.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Tomohiro Umeda, Yukari Hatanaka, Ayumi Sakai, Takami Tomiyama
Summary: The study found that intranasal administration of rifampicin significantly reduced the levels of alpha-synuclein oligomers in DLB model mice and improved cognitive function, suggesting that rifampicin may be a promising remedy for preventing neurodegenerative dementia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Sonja Fixemer, Corrado Ameli, Gael Hammer, Luis Salamanca, Oihane Uriarte Huarte, Chantal Schwartz, Jean-Jacques Gerardy, Naguib Mechawar, Alexander Skupin, Michel Mittelbronn, David S. Bouvier
Summary: Cellular alterations in the hippocampus lead to memory decline, a shared symptom in AD and DLB patients. The subregional deterioration patterns differ between AD and DLB, with CA1 being more severely affected in AD. Microglial activation may play a role in selective volume loss in the hippocampus.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Manuel Moreno-Valladares, Veronica Moncho-Amor, Iraide Bernal-Simon, Enaut Agirre-Iturrioz, Maria Alvarez-Satta, Ander Matheu
Summary: This case report highlights a complex interplay between norovirus infection, alpha-synuclein synthesis in the gastrointestinal mucosa, and Lewy pathology in the central nervous system in an older woman with unspecific symptoms. The presence of alpha-synuclein deposits and Lewy pathology support Braak's hypothesis about the pathogenic mechanisms underlying synucleinopathies, providing valuable insights into the understanding of these disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Hannah Bender, Simone A. Fietz, Franziska Richter, Milos Stanojlovic
Summary: The study in Thy1-aSyn mice reveals the impact of alpha-synuclein pathology on adult neurogenesis, showing an increase in early stage progenitors but no change in late stage progenitors and neurons. Increased astroglia marker in the hippocampus of transgenic mice was not specific to regions of adult neurogenesis, suggesting no commitment of additional early stage progenitors to astroglia lineage.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Matthieu Lilamand, Josue Clery, Agathe Vrillon, Francois Mouton-Liger, Emmanuel Cognat, Sinead Gaubert, Claire Hourregue, Matthieu Martinet, Julien Dumurgier, Jacques Hugon, Elodie Bouaziz-Amar, Claire Paquet
Summary: This study found that cerebrospinal fluid levels of alpha-synuclein differ significantly between DLB and AD, suggesting its potential as a biomarker for distinguishing between these two diseases. CSF alpha-synuclein is associated with other AD biomarkers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Makoto Timon Tanaka, Yasuo Miki, Conceicao Bettencourt, Taku Ozaki, Kunikazu Tanji, Fumiaki Mori, Akiyoshi Kakita, Koichi Wakabayashi
Summary: This study explored the involvement of Rubicon family proteins in synucleinopathies and found the participation of DEF8 in the formation of Lewy bodies. The protein levels of DEF8 were significantly increased in patients with PD and DLB, while Rubicon, Pacer, and DEF8 did not show immunoreactivity in patients with MSA. These results indicate the association of this protein family with dysregulation of autophagy in synucleinopathies.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Clinical Neurology
Alice Tisserand, Benjamin Cretin, Mary Mondino, Anne Botzung, Lea Sanna, Catherine Demuynck, Pierre Anthony, Candice Muller, Olivier Bousiges, Nathalie Philippi, Frederic Blanc
Summary: This study aimed to investigate the association between photophobia and dementia with Lewy bodies (DLB). The study found that photophobia was more frequent in DLB patients and was associated with decreased gray matter in the right precentral cortex and the eyelid motor region. This finding is important for understanding the pathological mechanism of DLB.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Review
Biochemistry & Molecular Biology
Noah J. Graves, Yann Gambin, Emma Sierecki
Summary: Like many neurodegenerative diseases, Parkinson's disease (PD) is characterized by the formation of proteinaceous aggregates in brain cells. Additionally, these aggregates are also found in other disorders, collectively referred to as synucleinopathies. Despite the diversity in pathologies and symptoms, aSyn aggregates are a common marker and potential driver of these diseases. This review compares PD, DLB, and MSA, highlighting the role of aSyn aggregates in each disorder and discussing the relationship between aSyn strains and the cellular environment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Joyce R. R. Chong, Yuek Ling Chai, Huayang Xing, Deron R. Herr, Markus R. Wenk, Paul T. Francis, Clive Ballard, Dag Aarsland, David L. Silver, Christopher P. P. Chen, Amaury Cazenave-Gassiot, Mitchell K. P. Lai
Summary: In this study, the authors found altered specific DHA-containing phospholipids in the cortex of patients with dementia with Lewy bodies (DLB) through phospholipidomics analysis. These alterations were associated with markers of neuropathological burden and synaptopathology. Furthermore, changes in the immunoreactivities of brain lysolipid DHA transporter and fatty acid binding protein were also observed in the DLB cortex.
Article
Geriatrics & Gerontology
Ying-Tsung Chen, Satoshi Orimo, Cheng-Yu Wei, Guang-Uei Hung, Shieh-Yueh Yang, Pai-Yi Chiu
Summary: Plasma alpha-synuclein and MDQ were found to be significantly higher in patients with DLB compared to the NC or AD groups. The novel SMDCS showed significantly improved accuracy for the clinical differentiation of DLB from AD or NC.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Neurosciences
Per Borghammer, Jacob Horsager, Katrine Andersen, Nathalie Van den Berge, Anna Raunio, Shigeo Murayama, Laura Parkkinen, Liisa Myllykangas
Summary: The aggregation of alpha-synuclein into inclusion bodies, known as Lewy pathology, is a key feature of Parkinson's disease and Dementia with Lewy bodies. Post mortem studies have shown that Lewy pathology follows two main distribution patterns in the brain, with some patients having pathogenic alpha-synuclein originating in the enteric nervous system and others originating inside the central nervous system.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Neurosciences
Vasileios Glykos, Miles A. Whittington, Fiona E. N. LeBeau
JOURNAL OF PHYSIOLOGY-LONDON
(2015)
Article
Neurosciences
Sabine Gretenkord, Adrian Rees, Miles A. Whittington, Sarah E. Gartside, Fiona E. N. LeBeau
JOURNAL OF NEUROPHYSIOLOGY
(2017)
Article
Clinical Neurology
Myrto Stylianou, Nicholas Murphy, Luis R. Peraza, Sara Graziadio, Ruth Cromarty, Alison Killen, John T. O' Brien, Alan J. Thomas, Fiona E. N. LeBeau, John-Paul Taylor
CLINICAL NEUROPHYSIOLOGY
(2018)
Article
Neurosciences
Emma Robson, Clare Tweedy, Nelson Manzanza, John-Paul Taylor, Peter Atkinson, Fiona Randall, Amy Reeve, Gavin J. Clowry, Fiona E. N. LeBeau
Article
Developmental Biology
Miles A. Whittington, Mark O. Cunningham, Fiona E. N. LeBeau, Claudia Racca, Roger D. Traub
DEVELOPMENTAL NEUROBIOLOGY
(2011)
Article
Neurosciences
David J. Cox, Claudia Racca, Fiona E. N. Lebeau
JOURNAL OF COMPARATIVE NEUROLOGY
(2008)
Article
Neurosciences
D. C. Haggerty, V. Glykos, N. E. Adams, F. E. N. Lebeau
Article
Multidisciplinary Sciences
Steven Middleton, Jozsi Jalics, Tillman Kispersky, Fiona E. N. LeBeau, Anita K. Roopun, Nancy J. Kopell, Miles A. Whittington, Mark O. Cunningham
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2008)
Article
Neurosciences
Anita K. Roopun, Fiona E. N. LeBeau, James Rammell, Mark O. Cunningham, Roger D. Traub, Miles A. Whittington
FRONTIERS IN NEURAL CIRCUITS
(2010)
Article
Biochemical Research Methods
Christoph Boergers, Giovanni Talei Franzesi, Fiona E. N. LeBeau, Edward S. Boyden, Nancy J. Kopell
PLOS COMPUTATIONAL BIOLOGY
(2012)
Review
Medicine, General & Internal
Zhe Kang Law, Carein Todd, Ramtin Mehraram, Julia Schumacher, Mark R. Baker, Fiona E. N. LeBeau, Alison Yarnall, Marco Onofrj, Laura Bonanni, Alan Thomas, John-Paul Taylor
Article
Neurosciences
Natalie E. Adams, Jason S. Sherfey, Nancy J. Kopell, Miles A. Whittington, Fiona E. N. LeBeau
Article
Neurosciences
Joanne E. Driver, Claudia Racca, Mark O. Cunningham, Stephen K. Towers, Ceri H. Davies, Miles A. Whittington, Fiona E. N. LeBeau
EUROPEAN JOURNAL OF NEUROSCIENCE
(2007)
Article
Neurosciences
Andrea Bibbig, Steven Middleton, Claudia Racca, Martin J. Gillies, Helen Garner, Fiona E. N. LeBeau, Ceri H. Davies, Miles A. Whittington
JOURNAL OF NEUROPHYSIOLOGY
(2007)