Article
Clinical Neurology
Zhe Long, Muireann Irish, David Foxe, John R. Hodges, Olivier Piguet, James R. Burrell
Summary: This study aimed to examine the clinical presentation of patients diagnosed with frontotemporal dementia-motor neuron disease (FTD-MND) in comparison to FTD subtypes and to clarify the heterogeneity of behavioral and language deficits in FTD-MND. Results showed that FTD-MND patients exhibited varied combinations of deficits and the frequency and severity of behavioral and language abnormalities were between those seen in the three FTD phenotypes. Cluster analysis identified three patterns of behavioral and language impairment in FTD-MND.
JOURNAL OF NEUROLOGY
(2021)
Review
Biochemistry & Molecular Biology
Raquel Garcia-Garcia, Laura Martin-Herrero, Laura Blanca-Pariente, Jesus Perez-Cabello, Cintia Roodveldt
Summary: ALS and FTD are the most common neurodegenerative diseases in adults, sharing clinical, genetic, and pathological similarities, characterized by progressive neuronal loss and chronic inflammation mediated by immune signaling kinases. The role of immune signaling kinases in determining neuroprotective or neurodegenerative states in ALS and FTD is crucial for understanding the underlying mechanisms of these disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neuroimaging
Ana Paula Arantes Bueno, Leonardo Cruz de Souza, Walter Hugo Lopez Pinaya, Antonio Lucio Teixeira, Laura Godoy Rousseff de Prado, Paulo Caramelli, Michael Hornberger, Joao Ricardo Sato
Summary: Amyotrophic lateral sclerosis and behavioural variant frontotemporal dementia are two distinct diseases with overlapping features, but with differences in episodic memory impairment and gray matter atrophy, especially in the Papez circuit, where the latter shows more significant changes compared to the former.
BRAIN IMAGING AND BEHAVIOR
(2021)
Article
Genetics & Heredity
C. Vinciguerra, A. Di Fonzo, E. Monfrini, D. Ronchi, S. Cuoco, G. Piscosquito, P. Barone, M. T. Pellecchia
Summary: This article describes a family with a novel MFN2 mutation, where the mother has ALS-frontotemporal dementia (FTD) clinical phenotype and the son has Charcot-Marie-Tooth disease type 2A (CMT2A). The study findings reveal heterogenous clinical manifestations in family members with the same MFN2 molecular defect. This is the first documented case of MFN2 mutation associated with ALS-FTD, expanding the range of MFN-related disorders.
FRONTIERS IN GENETICS
(2023)
Article
Clinical Neurology
Claudia S. Bauer, Rebecca N. Cohen, Francesca Sironi, Matthew R. Livesey, Thomas H. Gillingwater, J. Robin Highley, Daniel J. Fillingham, Ian Coldicott, Emma F. Smith, Yolanda B. Gibson, Christopher P. Webster, Andrew J. Grierson, Caterina Bendotti, Kurt J. De Vos
Summary: A GGGGCC hexanucleotide repeat expansion in the C9ORF72 gene is the main genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. This study shows that C9orf72 protein interacts with the synapsin family of synaptic vesicle proteins, and C9orf72 deficiency reduces the number of excitatory synapses and synapsin levels, leading to synaptic dysfunction.
ACTA NEUROPATHOLOGICA
(2022)
Article
Cell Biology
Sarah Pickles, Desiree Zanetti Alepuz, Yuka Koike, Mei Yue, Jimei Tong, Pinghu Liu, Yugui Zhou, Karen Jansen-West, Lillian M. M. Daughrity, Yuping Song, Michael DeTure, Bjoern Oskarsson, Neill R. R. Graff-Radford, Bradley F. F. Boeve, Ronald C. C. Petersen, Keith A. A. Josephs, Dennis W. W. Dickson, Michael E. E. Ward, Lijin Dong, Mercedes Prudencio, Casey N. N. Cook, Leonard Petrucelli
Summary: The limited treatments for neurodegenerative diseases such as FTD and ALS highlight the need for better understanding of their mechanisms and the development of disease-relevant models. Researchers have generated a novel CRISPRi knockin mouse to overcome the limitations of conventional knockout and transgenic mice. This model has been validated by confirming the reduced levels of STMN2 protein in FTD and has the potential for further research in understanding gene function and neurodegenerative diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Genetics & Heredity
Shiroh Miura, Shigeyoshi Hiruki, Tomohisa Okada, Satoko Itani Takei, Kensuke Senzaki, Yoko Okada, Masayuki Ochi, Yuki Tanabe, Hirofumi Ochi, Michiya Igase, Yasumasa Ohyagi, Hiroki Shibata
Summary: This study reported a 51-year-old Japanese female with frontotemporal dementia and amyotrophic lateral sclerosis. The presence of a variant in the valosin-containing protein gene was identified as the likely cause of the patient's symptoms through clinical and imaging examinations.
FRONTIERS IN GENETICS
(2023)
Review
Clinical Neurology
Jared S. Katzeff, Fiona Bright, Katherine Phan, Jillian J. Kril, Lars M. Ittner, Michael Kassiou, John R. Hodges, Olivier Piguet, Matthew C. Kiernan, Glenda M. Halliday, Woojin Scott Kim
Summary: This study explores and evaluates potential biomarkers for distinguishing frontotemporal dementia and amyotrophic lateral sclerosis, aiming to improve diagnosis and treatment for patients. The two diseases share common genetic and molecular features, with a lack of sensitive and specific biomarkers for diagnostic and disease surveillance purposes.
Article
Clinical Neurology
Jonathan D. Glass, Ramita Dewan, Jinhui Ding, J. Raphael Gibbs, Clifton Dalgard, Pamela J. Keagle, Shankaracharya, Alberto Garcia-Redondo, Bryan J. Traynor, Ruth Chia, John E. Landers
Summary: Intermediate CAG (polyQ) expansions in the ATXN2 gene are associated with amyotrophic lateral sclerosis (ALS). Expansions of >= 31 repeats increase the risk for ALS and even greater risk for ALS with frontotemporal dementia (FTD).
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)
Article
Neurosciences
Kyle J. Trageser, Eun-Jeong Yang, Chad Smith, Ruth Iban-Arias, Tatsunori Oguchi, Maria Sebastian-Valverde, Umar Haris Iqbal, Henry Wu, Molly Estill, Md Al Rahim, Urdhva Raval, Francis J. Herman, Yong Jie Zhang, Leonard Petrucelli, Giulio Maria Pasinetti
Summary: Hexanucleotide repeat expansions in C9orf72 gene cause frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS) and lead to the production of toxic dipeptide repeat (DPR) proteins, with poly(glycine-arginine) (GR) being the most toxic and accumulating in relevant brain regions. Neuroinflammation is a driving factor in the disease, and increased inflammasome-mediated neuroinflammation is observed in C9orf72 FTD/ALS mice, suggesting a role for HRE in innate immunity and the NLRP3 inflammasome as a potential therapeutic target.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Clinical Neurology
Miguel Tabuas-Pereira, Isabel Santana, Elizabeth Gibbons, Kimberly Paquette, Maria Rosario Almeida, Ines Baldeiras, Jose Bras, Rita Guerreiro
Summary: This study expands the research on genes known to cause FTD-ALS in the Portuguese population. The study found that variants in genes such as ERBB4, FUS, SETX, ANG, CHRNA4, and CHRNB4 may be associated with FTD.
FRONTIERS IN NEUROLOGY
(2022)
Review
Neurosciences
Jennilee M. Davidson, Roger S. Chung, Albert Lee
Summary: Investigations into the pathogenetic mechanisms of ALS and FTD have revealed shared dysregulated signaling pathways, with p62 playing a crucial role.
NEUROBIOLOGY OF DISEASE
(2022)
Review
Clinical Neurology
Stephanie L. Rayner, Alison Hogan, Jennilee M. Davidson, Flora Cheng, Luan Luu, Marco Morsch, Ian Blair, Roger Chung, Albert Lee
Summary: ALS is a common disease characterized by the degeneration of motor neurons in the brain and spinal cord, and is clinically linked to FTD dementia. Identifying gene mutations associated with ALS/FTD is valuable for understanding the disease process.
Review
Neurosciences
Layla T. Ghaffari, Davide Trotti, Aaron R. Haeusler, Brigid K. Jensen
Summary: ALS is a progressive neurodegenerative disease with heterogeneous clinical manifestations and lack of effective treatment. Cortical hyper-excitability is observed early in the disease and is associated with nucleotide repeat expansion in the C9ORF72 gene. ALS and FTD are part of a disease spectrum, both characterized by synaptic dysfunction.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)