Article
Clinical Neurology
Jolien Perneel, Masood Manoochehri, Edward D. Huey, Rosa Rademakers, Jill Goldman
Summary: Frontotemporal dementia (FTD) is the second-most common young-onset dementia. Variants in the TMEM106B gene have been proposed as modifiers of FTD disease risk, especially in progranulin (GRN) mutation carriers. This case report illustrates the importance of combining TMEM106B genotyping with GRN mutation screening to provide more appropriate genetic counseling and evaluate disease risk in GRN families.
FRONTIERS IN NEUROLOGY
(2023)
Article
Clinical Neurology
Rebecca R. Valentino, Michael G. Heckman, Patrick W. Johnson, Matthew C. Baker, Alexandra Soto-Beasley, Ronald L. Walton, Shunsuke Koga, Shanu F. Roemer, EunRan Suh, Ryan J. Uitti, John Q. Trojanowski, Murray Grossman, Vivianna M. Van Deerlin, Rosa Rademakers, Zbigniew K. Wszolek, Dennis W. Dickson, Owen A. Ross
Summary: The study aimed to investigate the association between stable polymorphisms defining mitochondrial haplogroups in mitochondrial DNA (mtDNA) and the risk of Pick disease. While no individual mtDNA haplogroups were significantly associated with Pick disease risk, some haplogroups like W and subhaplogroup H4 showed nominal associations with increased risk of Pick disease. This indicates that mtDNA variation may not be a direct driver of the disease, but could potentially influence disease susceptibility. Ongoing genetic assessments in larger cohorts of Pick disease are currently underway.
Article
Neurosciences
Karthick Natarajan, Jesper Eisfeldt, Maria Hammond, Jose Miguel Laffita-Mesa, Kalicharan Patra, Behzad Khoshnood, Linn Oijerstedt, Caroline Graff
Summary: The study identified an individual with a progranulin mutation who did not develop dementia symptoms, suggesting that restoring brain progranulin levels may prevent neurodegeneration. The results also indicated that in addition to previously identified modifier genes, epigenetic marks may contribute to increased progranulin expression in cases of reduced penetrance. These findings may inspire further research and new therapeutic approaches.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Clinical Neurology
Cristina Villa, Giacomina Rossi, Ilaria Bizzozero, Sara Prioni, Chiara Boiocchi, Federica Agosta, Elisa Canu, Massimo Filippi, Giorgio Giaccone, Paola Caroppo
Summary: This study describes the clinical characteristics of a new family carrying the Q336H MAPT mutation. The proband was diagnosed with semantic variant primary progressive aphasia (svPPA), while the proband's parent was diagnosed with Alzheimer's disease (AD). The study shows that this mutation is associated with svPPA and an AD-like phenotype, and there is significant clinical variability within affected individuals. Therefore, this gene should be analyzed in patients with svPPA.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Review
Immunology
Morgan Similuk, Taco Kuijpers
Summary: The overall disease burden of pediatric infection is high, with varying clinical outcomes. Inborn errors of immunity, which affect vulnerable children, have complex genetic and environmental causes. Recent advances in understanding these errors have improved diagnosis and treatment, but many questions remain regarding genetic and environmental contributions to phenotypic variation. It is important to integrate information to better understand the immune system and improve patient care.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Neurosciences
Yuxing Xia, Zhijuan Chen, Guilian Xu, David R. Borchelt, Jacob Ayers, Benoit Giasson
Summary: ALS is a progressive neurological disease caused by motor neuron degeneration, with SOD1 mutations leading to toxic aggregates in the brain and spinal cord. Monoclonal antibodies generated from SOD1 knockout mice can selectively detect denatured or aggregated SOD1, providing a potential tool for clinical diagnosis and passive immunotherapy for SOD1 ALS.
NEUROSCIENCE LETTERS
(2021)
Article
Multidisciplinary Sciences
Eanna B. Ryan, Jianhua Yan, Nimrod Miller, Sudarshan Dayanidhi, Yongchao C. Ma, Han-Xiang Deng, Teepu Siddique
Summary: Mutations in the CHCHD10 gene have been linked to various degenerative diseases, including ALS. Transgenic mice overexpressing an ALS-linked CHCHD10 mutation showed an abbreviated lifespan and exhibited pathology in the CNS, skeletal muscle, and cardiac tissue. The study provides insights into the pathogenesis of CHCHD10-related disorders, suggesting a contribution of CNS, skeletal muscle, and cardiac pathology to the disease.
Article
Multidisciplinary Sciences
Mariusz Berdynski, Przemyslaw Miszta, Krzysztof Safranow, Peter M. Andersen, Mitsuya Morita, Slawomir Filipek, Cezary Zekanowski, Magdalena Kuzma-Kozakiewicz
Summary: The study investigated the relations between SOD1 mutations and clinical presentation in ALS patients, identifying significant correlations between SOD1 mutations and clinical phenotype as well as associations between different types of mutations and clinical outcomes.
SCIENTIFIC REPORTS
(2022)
Article
Clinical Neurology
Helena Gossye, Sara Van Mossevelde, Anne Sieben, Maria Bjerke, Elisabeth Hendrickx Van de Craen, Julie van der Zee, Peter P. De Deyn, Jan De Bleecker, Jan Versijpt, Jenneke van den Ende, Olivier Deryck, Paul Bourgeois, Jean Christophe Bier, Maarten Goethals, Rik Vandenberghe, Sebastiaan Engelborghs, Christine Van Broeckhoven
Summary: The study investigates a pathogenic mutation leading to frontotemporal lobar degeneration and identifies a phenotypic spectrum ranging from behavioural variant FTD to Alzheimer's disease. It also describes the clinical and genetic characteristics of the mutation carriers and analyzes the neurocognitive, imaging, and biomarker characteristics.
Review
Clinical Neurology
Jacob I. Ayers, David R. Borchelt
Summary: familial amyotrophic lateral sclerosis (fALS) is caused by protein mutations that mediate neurodegenerative processes and share similarities with prion diseases. ALS is a heterogeneous disease with most cases being sporadic, but inherited forms may lead to the presence of distinct conformations resembling prion strains. Studies are being conducted to understand how the tertiary structure of ALS-linked proteins may impact the disease phenotype.
ACTA NEUROPATHOLOGICA
(2021)
Article
Neurosciences
Ileana Lorenzini, Eric Alsop, Jennifer Levy, Lauren M. Gittings, Deepti Lall, Benjamin E. Rabichow, Stephen Moore, Ryan Pevey, Lynette M. Bustos, Camelia Burciu, Divya Bhatia, Mo Singer, Justin Saul, Amanda McQuade, Makis Tzioras, Thomas A. Mota, Amber Logemann, Jamie Rose, Sandra Almeida, Fen-Biao Gao, Michael Marks, Christopher J. Donnelly, Elizabeth Hutchins, Shu-Ting Hung, Justin Ichida, Robert Bowser, Tara Spires-Jones, Mathew Blurton-Jones, Tania F. Gendron, Robert H. Baloh, Kendall Van Keuren-Jensen, Rita Sattler
Summary: In this study, researchers investigate the role of non-neuronal cells, specifically microglia, in C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). They find that iPSC-derived microglia from C9orf72 ALS/FTD patients exhibit pathological features and perform similar functions as healthy control microglia. Transcriptomic analysis reveals selective transcriptional changes related to neuroinflammation and neurodegeneration in diseased microglia. The findings suggest that a diseased microenvironment is required to induce phenotypic changes in microglia and the associated neuronal dysfunction in C9orf72 ALS/FTD.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Review
Chemistry, Multidisciplinary
Benjamin G. Trist, James B. Hilton, Dominic J. Hare, Peter J. Crouch, Kay L. Double
Summary: Cu/Zn superoxide dismutase (SOD1) is a crucial antioxidant enzyme in eukaryotic life, with mitochondrial aerobic respiration increasing cellular superoxide production and reliance on SOD1. Diseases of the central nervous system often involve disruptions in SOD1 biology, revealing complex molecular characteristics that differentiate healthy from disease-contributing SOD1 proteins. This review highlights current knowledge of SOD1 biology, from genetics to protein function and stability.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Cell Biology
Dayan B. Goodenowe, Jonathan Haroon, Mitchel A. Kling, Margaret Zielinski, Kennedy Mahdavi, Barshen Habelhah, Leah Shtilkind, Sheldon Jordan
Summary: This study investigated the effects of escalating oral dosing of DHA-AAG on blood serum plasmalogen, non-plasmalogen phospholipids, and oxidative stress biomarkers. The results showed that DHA plasmalogen levels increased with increasing dose and remained significantly elevated at all treatment doses and durations. Additionally, DHA-AAG supplementation normalized oxidative stress biomarkers and improved cognition and mobility.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Geriatrics & Gerontology
Merel O. Mol, Jeroen G. J. van Rooij, Tsz H. Wong, Shamiram Melhem, Annemieke J. M. H. Verkerk, Anneke J. A. Kievit, Rick van Minkelen, Rosa Rademakers, Cyril Pottier, Laura Donker Kaat, Harro Seelaar, John C. van Swieten, Elise G. P. Dopper
Summary: The study found a significant proportion of pathogenic or likely pathogenic genetic variants in FTD patients, including some newly discovered variants. Common variant genes include C9orf72, MAPT, GRN, and TARDBP, while other pathogenic variants were found in VCP, TBK1, PSEN1, etc. Patients without identified genetic cause showed a wide range of clinical and pathological variability.
NEUROBIOLOGY OF AGING
(2021)
Review
Clinical Neurology
Daphne Stam, Simon Rosseel, Francois-Laurent De Winter, Maarten J. A. Van den Bossche, Mathieu Vandenbulcke, Jan Van den Stock
Summary: This study examines deficits in social cognition in frontotemporal dementia (FTD) and Alzheimer's disease (AD) through qualitative synthesis and meta-analysis of facial expression recognition studies. The results show that both FTD and AD are associated with deficits in facial expression recognition, with FTD having more pronounced deficits compared to AD. Overall emotion recognition was most frequently impaired in both disorders, with anger recognition being most affected in FTD and fear recognition in AD. Verbal categorization was the most commonly used task, but matching or intensity rating tasks may be more specific. Studies from Oceania revealed larger deficits, while non-emotional control tasks were more impacted by AD than FTD. These findings highlight the social cognitive phenotype of FTD and AD and suggest the importance of social cognition assessment in late-life neuropsychiatric disorders.
JOURNAL OF NEUROLOGY
(2023)