Review
Biochemistry & Molecular Biology
Merel O. Mol, Suzanne S. M. Miedema, John C. van Swieten, Jeroen G. J. van Rooij, Elise G. P. Dopper
Summary: FTLD is a neurodegenerative disorder with major impact on patients and their families, mainly characterized by TDP-43 proteinopathy. The exact mechanisms driving FTLD-TDP remain largely unknown, but proteomic approaches hold promise to elucidate pathogenic molecular and cellular alterations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Ryota Kobayashi, Shinobu Kawakatsu, Makoto Ohba, Daichi Morioka, Masafumi Kanoto, Koichi Otani
Summary: Abnormal findings on dopamine transporter single photon emission computed tomography were observed in patients with FTLD-MND, which may manifest even before the onset of MND symptoms.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Clinical Neurology
Lauren M. Forgrave, Kyung-Mee Moon, Jordan E. Hamden, Yun Li, Phoebe Lu, Leonard J. Foster, Ian R. A. Mackenzie, Mari L. DeMarco
Summary: Biomarkers of TDP-43 pathology are needed to differentiate FTLD-TDP from related disorders. Using high-resolution mass spectrometry, we identified truncated TDP-43 as a potential biomarker with high diagnostic accuracy for FTLD-TDP.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Kasper Katisko, Nadine Huber, Tarja Kokkola, Paivi Hartikainen, Johanna Kruger, Anna-Leena Heikkinen, Veera Paananen, Ville Leinonen, Ville E. Korhonen, Seppo Helisalmi, Sanna-Kaisa Herukka, Valentina Cantoni, Yasmine Gadola, Silvana Archetti, Anne M. Remes, Annakaisa Haapasalo, Barbara Borroni, Eino Solje
Summary: This study found that total levels of TDP-43 in the serum are decreased in patients with frontotemporal dementia (FTD), especially in those with C9orf72 repeat expansion or concomitant motoneuron disease (FTD-MND) phenotype. Serum-based measurement of TDP-43 may serve as a useful tool for predicting TDP-43 neuropathology associated with C9orf72 repeat expansion and FTD-MND in future diagnostics and intervention studies.
ALZHEIMERS RESEARCH & THERAPY
(2022)
Review
Clinical Neurology
Arenn F. Carlos, Keith A. Josephs
Summary: This paper reviews how FTLD-TDP was established and defined clinically and neuropathologically throughout the past century.
JOURNAL OF NEUROLOGY
(2022)
Article
Neurosciences
Luigi Fiondella, Priya A. Gami-Patel, Christian Blok, Annemieke J. M. Rozemuller, Jeroen J. M. Hoozemans, Yolande A. L. A. Pijnenburg, Marta Scarioni, Anke Dijkstra
Summary: This study explores the occurrence and nature of movement disorders (MD) in FTLD-TDP brain donors. It reveals that 17% of FTLD-TDP patients develop MD, presenting as symmetric akinetic-rigid parkinsonism or CBS. The research also suggests that the higher TDP-43 burden in the substantia nigra (SN) may be related to the presence of MD in FTLD-TDP patients, while nigral neuronal density does not significantly differ between patients with and without MD.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Medicine, General & Internal
Roberta Cascella, Martina Banchelli, Seyyed Abolghasem Ghadami, Diletta Ami, Maria Cristina Gagliani, Alessandra Bigi, Tommaso Staderini, Davide Tampellini, Katia Cortese, Cristina Cecchi, Antonino Natalello, Hadi Adibi, Paolo Matteini, Fabrizio Chiti
Summary: This study investigated the morphological, structural, and tinctorial properties of TAR DNA-binding protein 43 (TDP-43) inclusions in neuroblastoma x spinal cord 34 (NSC-34) cells. The results showed that TDP-43 inclusions did not exhibit amyloid properties and lacked cross-beta structure and fibrillar morphology. These findings suggest that TDP-43 has a low propensity to form amyloid fibrils and instead forms other types of inclusions.
ANNALS OF MEDICINE
(2023)
Article
Neurosciences
Alba Cervantes Gonzalez, David J. Irwin, Daniel Alcolea, Corey T. McMillan, Alice Chen-Plotkin, David Wolk, Sonia Sirisi, Oriol Dols-Icardo, Marta Querol-Vilaseca, Ignacio Illan-Gala, Miguel Angel Santos-Santos, Juan Fortea, Edward B. Lee, John Q. Trojanowski, Murray Grossman, Alberto Lleo, Olivia Belbin
Summary: The study found an association between synaptic proteins and pathological burden and cognitive performance in frontotemporal lobar degeneration (FTLD) patients. These synaptic panels have the potential to differentiate FTLD neuropathologic subtypes and serve as surrogate markers for cognitive performance in future clinical trials.
MOLECULAR NEURODEGENERATION
(2022)
Article
Neurosciences
Sarah Pickles, Tania F. Gendron, Yuka Koike, Mei Yue, Yuping Song, Jennifer M. Kachergus, J. Shi, Michael DeTure, E. Aubrey Thompson, Bjorn Oskarsson, Neill R. Graff-Radford, Bradley F. Boeve, Ronald C. Petersen, Zbigniew K. Wszolek, Keith A. Josephs, Dennis W. Dickson, Leonard Petrucelli, Casey N. Cook, Mercedes Prudencio
Summary: This study found that the cerebellum plays an important role in FTLD-TDP, with decreased levels of TDP-43 protein and increased levels of truncated STMN2 transcripts, indicating TDP-43 dysfunction. Lower cerebellar TDP-43 was also associated with younger age at disease onset. These findings suggest that further investigation into the role of the cerebellum in FTLD-TDP is warranted.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Michael W. Baughn, Ze'ev Melamed, Jone Lopez-Erauskin, Melinda S. Beccari, Karen Ling, Aamir Zuberi, Maximilliano Presa, Elena Gonzalo-Gil, Roy Maimon, Sonia Vazquez-Sanchez, Som Chaturvedi, Mariana Bravo-Hernandez, Vanessa Taupin, Stephen Moore, Jonathan W. Artates, Eitan Acks, I. Sandra Ndayambaje, Ana R. Agra de Almeida Quadros, Paayman Jafar-Nejad, Frank Rigo, C. Frank Bennett, Cathleen Lutz, Clotilde Lagier-Tourenne, Don W. Cleveland
Summary: Loss of nuclear TDP-43 is a key factor in neurodegeneration. The mislocalization of TDP-43 leads to cryptic splicing and polyadenylation of pre-mRNAs encoding stathmin-2. Targeting dCasRx or ASOs can suppress cryptic splicing, restoring axonal regeneration and stathmin-2-dependent lysosome trafficking.
Review
Neurosciences
Katherine E. Prater, Caitlin S. Latimer, Suman Jayadev
Summary: Since its discovery in 2006, TDP-43 has been a key focus in research on neurodegenerative diseases, contributing to cognitive impairment and potentially potentiating other proteinopathies. However, there are still gaps in understanding TDP-43 driven mechanisms across different cell types, and further research is needed on the relationship between TDP-43 and glial pathology.
Review
Neurosciences
Hulya Ulugut, Anke A. Dijkstra, Marta Scarioni, Netherlands Brain Bank, Frederik Barkhof, Philip Scheltens, Annemieke J. M. Rozemuller, Yolande A. L. Pijnenburg
Summary: Despite being considered a right-sided variant of svPPA, rtvFTD may demonstrate either frontotemporal or temporal evolution. The most common underlying pathology is FTLD-TDP type C, but other pathologies such as Tau-MAPT and FTLD-TDP type A and B are also present in a significant percentage of rtvFTD cases. Additionally, motor neuron or corticospinal tract degeneration was observed in a portion of rtvFTD patients.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Clinical Neurology
Marina Buciuc, Jennifer L. Whitwell, Matthew C. Baker, Rosa Rademakers, Dennis W. Dickson, Keith A. Josephs
Summary: The burden of TDP-43 inclusions was assessed in elderly patients with genetic FTLD-TDP and compared to sporadic cases with TDP-43. It was found that patients with genetic FTLD-TDP had a higher burden in the entorhinal cortex compared to AD-TDP, but no significant difference in the middle frontal cortex burden.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2021)
Article
Clinical Neurology
Allegra Kawles, Yasushi Nishihira, Alex Feldman, Nathan Gill, Grace Minogue, Rachel Keszycki, Christina Coventry, Callen Spencer, Jaclyn Lilek, Kaouther Ajroud, Giovanni Coppola, Rosa Rademakers, Emily Rogalski, Sandra Weintraub, Hui Zhang, Margaret E. Flanagan, Eileen H. Bigio, M-Marsel Mesulam, Changiz Geula, Qinwen Mao, Tamar Gefen
Summary: This study provides a detailed characterization of the pathological distribution of TDP-43 and gliosis in FTLD-TDP-type C, and investigates the relationship between inclusions and neurodegeneration. The findings suggest an inverse relationship between the extent of TDP-positive inclusions and neuronal loss.
Article
Neurosciences
Shunsuke Koga, Aya Murakami, Alexandra I. Soto-Beasley, Ronald L. Walton, Matthew C. Baker, Monica Castanedes-Casey, Keith A. Josephs, Owen A. Ross, Dennis W. Dickson
Summary: Frontotemporal lobar degeneration (FTLD) is a group of disorders characterized by degeneration of the frontal and temporal lobes, leading to decline in language, behavior, and motor function. In this report, a mixed neurodegenerative disease with features of diffuse argyrophilic grain disease (AGD), TDP-43 proteinopathy, and neuronal intermediate filament inclusion disease was observed in an 87-year-old woman. This case emphasizes the importance of considering multiple proteinopathies in the diagnosis of neurodegenerative diseases.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Clinical Neurology
O. Lindberg, P. Ostberg, B. B. Zandbelt, J. Oberg, Y. Zhang, C. Andersen, J. C. L. Looi, N. Bogdanovic, L. -O Wahlund
AMERICAN JOURNAL OF NEURORADIOLOGY
(2009)
Article
Clinical Neurology
J. C. L. Looi, L. Svensson, O. Lindberg, B. B. Zandbelt, P. Ostberg, E. Orndahl, L. -O. Wahlund
AMERICAN JOURNAL OF NEURORADIOLOGY
(2009)
Article
Audiology & Speech-Language Pathology
Monica Blom Johansson, Marianne Carlsson, Per Ostberg, Karin Sonnander
Article
Audiology & Speech-Language Pathology
Monica Blom Johansson, Marianne Carlsson, Per Ostberg, Karin Sonnander
Article
Clinical Neurology
Martin Cederlof, Sarah E. Bergen, Niklas Langstrom, Henrik Larsson, Marcus Boman, Nick Craddock, Per Ostberg, Sebastian Lundstrom, Arvid Sjolander, Klas Nordlind, Mikael Landen, Paul Lichtenstein
Article
Neurosciences
Olof Lindberg, Mark Walterfang, Jeffrey C. L. Looi, Nikolai Malykhin, Per Ostberg, Bram Zandbelt, Martin Styner, Beatriz Paniagua, Dennis Velakoulis, Eva Orndahl, Lars-Olof Wahlund
JOURNAL OF ALZHEIMERS DISEASE
(2012)
Article
Neurosciences
Mark Walterfang, Eileen Luders, Jeffrey C. L. Looi, Priya Rajagopalan, Dennis Velakoulis, Paul M. Thompson, Olof Lindberg, Per Ostberg, Love E. Nordin, Leif Svensson, Lars-Olof Wahlund
JOURNAL OF ALZHEIMERS DISEASE
(2014)
Article
Audiology & Speech-Language Pathology
Per Ostberg, Viktoria Hansson, Sofia Haagg
LOGOPEDICS PHONIATRICS VOCOLOGY
(2012)
Article
Neurosciences
Jeffrey Chee Leong Looi, Mark Walterfang, Martin Styner, Leif Svensson, Olof Lindberg, Per Ostberg, Lisa Botes, Eva Orndahl, Phyllis Chua, Rajeev Kumar, Dennis Velakoulis, Lars-Olof Wahlund
Article
Clinical Neurology
Jeffrey Chee Leong Looi, Mark Walterfang, Martin Styner, Marc Niethammer, Leif Anders Svensson, Olof Lindberg, Per Ostberg, Lisa Botes, Eva Orndahl, Phyllis Chua, Dennis Velakoulis, Lars-Olof Wahlund
PSYCHIATRY RESEARCH-NEUROIMAGING
(2011)
Article
Geriatrics & Gerontology
Olof Lindberg, Eric Westman, Sari Karlsson, Per Ostberg, Leif A. Svensson, Andrew Simmons, Lars-Olof Wahlund
FRONTIERS IN AGING NEUROSCIENCE
(2012)
Article
Psychology, Multidisciplinary
Sven-Erik Fernaeus, Per Ostberg, Lars-Olof Wahlund, Ake Hellstrom
SCANDINAVIAN JOURNAL OF PSYCHOLOGY
(2014)
Article
Psychology, Clinical
M. Cederlof, P. Ostberg, E. Pettersson, H. Anckarsater, C. Gumpert, S. Lundstrom, P. Lichtenstein
PSYCHOLOGICAL MEDICINE
(2014)
Article
Psychology, Multidisciplinary
Sven-Erik Fernaeus, Per Ostberg, Lars-Olof Wahlund
SCANDINAVIAN JOURNAL OF PSYCHOLOGY
(2013)