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)
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)
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
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
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)
Review
Biochemistry & Molecular Biology
Alistair Wood, Yuval Gurfinkel, Nicole Polain, Wesley Lamont, Sarah Lyn Rea
Summary: ALS and FTLD are neurodegenerative disorders with pathological, clinical, and genetic overlaps. The primary pathological protein, TDP-43, is observed in aggregates in affected tissues in majority of cases. Disease pathogenesis involves changes in RNA splicing, abnormal stress granules, mitochondrial dysfunction, and other cellular processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Jorge Garcia Morato, Friederike Hans, Felix von Zweydorf, Regina Feederle, Simon J. Elsasser, Angelos A. Skodras, Christian Johannes Gloeckner, Emanuele Buratti, Manuela Neumann, Philipp J. Kahle
Summary: TDP-43 is a nucleic acid binding protein that plays a role in the pathogenesis of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Post-translational modifications and acetylation of TDP-43 affect its interaction with RNA and its cellular localization. This study found that different lysine acetylations of TDP-43 modulate its nuclear import, RNA binding, and phase separation, suggesting regulatory mechanisms for TDP-43 pathogenesis.
NATURE COMMUNICATIONS
(2022)
Review
Cell Biology
Non-Nuoc Tran, Byung-Hoon Lee
Summary: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases associated with the abnormal aggregation of TDP-43. The ubiquitinating and deubiquitinating pathways may modulate the pathogenicity and toxicity of TDP-43 through mechanisms such as protein stability and translocation. Understanding these mechanisms could lead to the development of targeted therapies for ALS and FTD.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Clinical Neurology
Daniel T. Ohm, Katheryn A. Q. Cousins, Sharon X. Xie, Claire Peterson, Corey T. McMillan, Lauren Massimo, Katya Raskovsky, David A. Wolk, Vivianna M. Van Deerlin, Lauren Elman, Meredith Spindler, Andres Deik, John Q. Trojanowski, Edward B. Lee, Murray Grossman, David J. Irwin
Summary: This study found that FTLD-tau and FTLD-TDP accumulate pathology in different cortical layers, with lower layers predominantly affected in FTLD-tau and upper layers predominantly affected in FTLD-TDP. Additionally, the ratios of layer pathology were related to WM pathology and regional severity in FTLD-tau, but not in FTLD-TDP. Higher ratios of layer pathology were associated with greater cognitive impairment in FTLD-tau, but not in FTLD-TDP.
ACTA NEUROPATHOLOGICA
(2022)
Article
Medicine, Research & Experimental
Yoshiaki Yamanaka, Tamami Miyagi, Yuichiro Harada, Masahiko Kuroda, Kohsuke Kanekura
Summary: The study presents a novel chemically oligomerizable TDP-43 system that mimics ALS pathology and sheds light on the mechanisms underlying the aggregation and mislocalization of TDP-43.
LABORATORY INVESTIGATION
(2021)
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.
Article
Biochemistry & Molecular Biology
Kunikazu Tanji, Fumiaki Mori, Fumiyuki Shirai, Takehiro Fukami, Hiroyuki Seimiya, Jun Utsumi, Akiyoshi Kakita, Koichi Wakabayashi
Summary: Research has shown that tankyrase inhibitors can suppress the formation of TDP-43 protein aggregates and reduce the levels of tankyrase protein in neuronal cytoplasmic inclusions, potentially protecting against TDP-43 toxicity.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
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)
Review
Biochemistry & Molecular Biology
Han-Jou Chen, Jacqueline C. Mitchell
Summary: TDP-43 protein is strongly linked to the pathogenesis of neurodegenerative disorders, and while mutations in the TARDBP gene may cause disease in a small subset of patients, TDP-43 proteinopathy is present in a majority of cases. Cellular functions such as nucleocytoplasmic transport, protein homeostasis, RNA interactions, and cellular stress play key roles in TDP-43 pathogenesis, with evidence suggesting aggregation-prone TDP-43 can be transmitted intercellularly, contributing to disease spread.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Senthil T. Kumar, Sergey Nazarov, Silvia Porta, Niran Maharjan, Urszula Cendrowska, Malek Kabani, Francesco Finamore, Yan Xu, Virginia M. -Y. Lee, Hilal A. Lashuel
Summary: Reconstitution of TDP-43 filaments with sequence and morphological features similar to those found in the brain reveals a new mechanism for the formation and propagation of pathology in amyotrophic lateral sclerosis and other neurodegenerative diseases.
NATURE NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Ke-Liang Chen, He Wang, Gui-Xian Zhao, Lei Wei, Yu-Yuan Huang, Shi-Dong Chen, Jian Sun, Qiang Dong, Mei Cui, Jin-Tai Yu
Summary: A novel homozygous RNF216 p.E650X mutation causing Gordon Holmes syndrome was identified in this study, expanding the genetic knowledge of GHS and extending the ethnic distribution of RNF216 mutations.
JOURNAL OF MOLECULAR NEUROSCIENCE
(2022)
Article
Clinical Neurology
Jia-Hui Hou, Ya-Nan Ou, Wei Xu, Peng-Fei Zhang, Lan Tan, Jin-Tai Yu
Summary: This study found that peripheral immune cells and the ratio of these cells were associated with cognitive function, neuroimaging, and AD pathology. These associations may be mediated by beta-amyloid and tau pathology.
ALZHEIMERS RESEARCH & THERAPY
(2022)
Article
Medicine, Research & Experimental
Bang-Sheng Wu, Shu-Fen Chen, Shu-Yi Huang, Ya-Nan Ou, Yue-Ting Deng, Shi-Dong Chen, Qiang Dong, Jin-Tai Yu
Summary: By integrating multidimensional data, we identified causal genes in the pathogenesis of small-vessel stroke (SVS), offering hints for future biological and therapeutic studies.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Neurosciences
Shu-Yu Liang, Zuo-Teng Wang, Lan Tan, Jin-Tai Yu
Summary: This article introduces the function and dysfunction of microtubule-associated protein tau in the central nervous system and discusses its role in neurodegenerative diseases, tau phosphorylation-related enzymes and proteins, and its relationship with cell dysfunction. The study of tau neurotoxicity provides new directions for the treatment of tauopathies.
MOLECULAR NEUROBIOLOGY
(2022)
Review
Neurosciences
Yi Zhang, Kai-Min Wu, Liu Yang, Qiang Dong, Jin-Tai Yu
Summary: In this article, emerging knowledge on tauopathies from clinical, pathological, genetic, and experimental studies is synthesized to accelerate the development of therapeutics for these diseases. The focus is on depicting pathological characteristics, identifying biomarkers, elucidating the underlying pathogenesis for early diagnosis, and the development of disease-modifying therapies.
MOLECULAR NEURODEGENERATION
(2022)
Article
Environmental Sciences
He-Ying Hu, Ya-Hui Ma, Yue-Ting Deng, Ya-Nan Ou, Wei Cheng, Jian-Feng Feng, Lan Tan, Jin-Tai Yu
Summary: This study found an association between residential greenness and dementia incidence, indicating that increasing greenspace can reduce the risk of dementia. The protective effect of greenness may be mediated through the reduction of particulate air pollution.
ENVIRONMENTAL RESEARCH
(2023)
Review
Clinical Neurology
Na Zhang, Ke-Liang Chen, Yu-Yuan Huang, Shu-Fen Chen, Qiang Dong, Lan Tan, Jin-Tai Yu
CLINICAL NEUROLOGY AND NEUROSURGERY
(2023)
Article
Neurosciences
Zuo-Teng Wang, Yan Fu, Shi-Dong Chen, Yu-Yuan Huang, Ya-Hui Ma, Yan-Jiang Wang, Lan Tan, Jin-Tai Yu
Summary: This study is the first to identify significant associations between TREM1 rs2062323 and AD risk. The rs2062323T may be involved in AD by regulating the expression of TREM1, TREML1, TREM2, and sTREM2. The TREM family is expected to be a potential therapeutic target for AD.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Clinical Neurology
Yan Fu, Yan Sun, Zhi-Bo Wang, Dan-Dan Zhang, Lan Tan, Jian-Feng Feng, Wei Cheng, Jin-Tai Yu
Summary: This study used the American Heart Association's Life's Simple 7 (LS7) metric to define cardiovascular and brain health and found that ideal LS7 cardiovascular health factors are associated with both macrostructural and microstructural markers of brain health. The results suggest that better LS7 profiles are linked to better brain health.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yan Sun, Yu Guo, Hong-Qi Li, Lan Tan, Jian-Feng Feng, Wei Cheng, Jin-Tai Yu
Summary: White matter hyperintensities (WMH) are strongly associated with stroke, dementia, and early mortality. This study investigated the relationship between WMH and circulating metabolites in a large sample of individuals from the UK Biobank. The results showed that several metabolites, including high-density lipoprotein (HDL), fatty acids, and glycoprotein acetyls, were associated with WMH. Age and sex also had a significant influence on these associations. The findings suggest that specific metabolomic features accompany WMH and may provide insights into the implications of WMH in different populations.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Geriatrics & Gerontology
Yu He, Shu-Yi Huang, Hui-Fu Wang, Wei Zhang, Yue-Ting Deng, Ya-Ru Zhang, Qiang Dong, Jian-Feng Feng, Wei Cheng, Jin-Tai Yu
Summary: Cohort studies have shown inconsistent associations between omega-3 polyunsaturated fatty acids (n-3 PUFA) or fish oil and dementia risk. This study included a large number of participants and found that higher plasma levels of PUFA and fish oil supplementation were associated with a lower risk of developing dementia.
Article
Biochemistry & Molecular Biology
Shu-Yi Huang, Ya-Ru Zhang, Liu Yang, Yu-Zhu Li, Bang-Sheng Wu, Shi-Dong Chen, Jian-Feng Feng, Qiang Dong, Wei Cheng, Jin-Tai Yu
Summary: Identifying circulating metabolites associated with dementia, cognition, and brain volume could provide new insights into the pathogenesis of dementia. This cohort study found 26 metabolites associated with incident dementia, including specific associations with Alzheimer's disease (AD) and vascular dementia (VD). Circulating levels of certain lipoproteins were found to be associated with the risk of AD and AD phenotypes, while another lipoprotein was associated with the risk of VD.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Ji-Yun Cheng, Yue-Ting Deng, Jin-Tai Yu
Summary: Through a more robust analysis, we found potential associations between circulating levels of amino acids and the risk of neurodegenerative diseases. Increase in circulating levels of Glutamine (Gln) was associated with lower risk of Alzheimer's disease (AD), while increase in circulating levels of Leucine (Leu) was associated with lower risk of Parkinson's disease (PD). Replication tests further confirmed the potential association between circulating Gln levels and AD risk.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Neurosciences
Wei-Shi Liu, Ya-Ru Zhang, Yi-Jun Ge, Hui-Fu Wang, Wei Cheng, Jin-Tai Yu
Summary: This study identified the association between TREM2, temporal lobe, and AD using genetic and transcriptomic data, and explored the complex associations among inflammation, brain structure, and neurodegenerative disorders, particularly AD.
MOLECULAR NEUROBIOLOGY
(2023)
Review
Neurosciences
Hai-Shan Jiao, Peng Yuan, Jin-Tai Yu
Summary: Mutations in the TMEM106B gene are risk factors for various neurodegenerative diseases. Previous understanding of the underlying mechanism focused on the impairment of lysosome biogenesis caused by TMEM106B loss-of-function. However, mutations in TMEM106B increase its expression level, thus the molecular process linking these mutations to the apparent disruption in TMEM106B function remains mysterious.
MOLECULAR NEURODEGENERATION
(2023)
