Article
Clinical Neurology
Parichita Choudhury, Jonathan Graff-Radford, Jeremiah A. Aakre, Lincoln Wurtz, David S. Knopman, Neill R. Graff-Radford, Kejal Kantarci, Leah K. Forsberg, Julie A. Fields, Otto Pedraza, Qin Chen, Toji Miyagawa, Gregory S. Day, Philip Tipton, Rodolfo Savica, Hugo Botha, Christian Lachner, Brynn Dredla, R. Ross Reichard, Ronald C. Petersen, Dennis W. Dickson, Bradley F. Boeve, Tanis J. Ferman
Summary: An earlier onset of DLB was associated with men, RBD, and Lewy body disease without neocortical tangles. Women with DLB tended to be older, more cognitively impaired, less likely to have RBD, diagnosed later, and more likely to have neocortical tangles.
ALZHEIMERS & DEMENTIA
(2022)
Article
Clinical Neurology
Duygu Tosun, Ozlem Yardibi, Tammie L. S. Benzinger, Walter A. Kukull, Colin L. Masters, Richard J. Perrin, Michael W. Weiner, Arthur Simen, Adam J. Schwarz, lzheimers Dis Neuroimaging Initiative
Summary: In this study, a multilabel non-ADNC classifier using MRI signatures was developed for the identification of non-Alzheimer's disease neuropathological changes. The model showed high accuracy in distinguishing TDP-43, LBD, and CAA, outperforming reference models without MRI and ADNC biomarkers. Considering non-ADNC decreased the required sample size to detect cognitive decline.
ALZHEIMERS & DEMENTIA
(2023)
Article
Multidisciplinary Sciences
Dorit Trudler, Kristopher L. Nazor, Yvonne S. Eisele, Titas Grabauskas, Nima Dolatabadi, James Parker, Abdullah Sultan, Zhenyu Zhong, Marshall S. Goodwin, Yona Levites, Todd E. Golde, Jeffery W. Kelly, Michael R. Sierks, Nicholas J. Schork, Michael Karin, Rajesh Ambasudhan, Stuart A. Lipton
Summary: Parkinson's disease is associated with the accumulation of alpha-synuclein and activation of microglia, potentially leading to neuronal death. This study shows that alpha-synuclein can activate NLRP3 inflammasome in human microglia and that alpha-synuclein-antibody complexes can exacerbate inflammation in a human context.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Clinical Neurology
Jeremy C. S. Johnson, Charles R. Marshall, Rimona S. Weil, Doris-Eva Bamiou, Chris J. D. Hardy, Jason D. Warren
Summary: The association between hearing impairment and dementia poses a significant public health challenge, with potential for earlier diagnosis and prevention. Neurodegenerative pathologies are predicted to target the auditory brain and damage hearing function early. It is important to reconsider the role of auditory cognitive function in dementia and develop new auditory tests for early diagnosis.
Article
Clinical Neurology
Jeremy C. S. Johnson, Charles R. Marshall, Rimona S. Weil, Doris-Eva Bamiou, Chris J. D. Hardy, Jason D. Warren
Summary: The relationship between hearing impairment and dementia highlights the crucial role of the auditory brain in cognitive function, suggesting potential opportunities for early diagnosis and management strategies. Research emphasizes the importance of auditory cognitive function in neurodegenerative dementias, calling for the development of novel auditory testing methods and early diagnosis strategies.
Article
Biochemistry & Molecular Biology
Ilaria Palmieri, Tino Emanuele Poloni, Valentina Medici, Susanna Zucca, Annalisa Davin, Orietta Pansarasa, Mauro Ceroni, Livio Tronconi, Antonio Guaita, Stella Gagliardi, Cristina Cereda
Summary: The study compared two cases of different forms of dementia, highlighting similarities and differences in pathology, genetics, and transcriptomics, emphasizing the important role of transcriptome profiling in understanding the pathogenesis of AD and LBD.
Article
Clinical Neurology
John L. Robinson, Sharon X. Xie, Daniel R. Baer, EunRan Suh, Vivianna M. Van Deerlin, Nicholas J. Loh, David J. Irwin, Corey T. McMillan, David A. Wolk, Alice Chen-Plotkin, Daniel Weintraub, Theresa Schuck, Virginia M. Y. Lee, John Q. Trojanowski, Edward B. Lee
Summary: In this retrospective study, the incidence of 10 pathologies in neurodegenerative disease (ND) and normal aging was examined, with up to seven pathologies observed concurrently resulting in 161 different combinations. The presence of multiple additive pathologies was associated with factors such as longer disease duration, clinical dementia, older age, and APOE e4 status.
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)
Article
Biochemistry & Molecular Biology
Melina J. Lim, Suelen L. Boschen, Aishe Kurti, Monica Castanedes Casey, Virginia R. Phillips, John D. Fryer, Dennis Dickson, Karen R. Jansen-West, Leonard Petrucelli, Marion Delenclos, Pamela J. Mclean
Summary: The study aimed to evaluate whether the overexpression of alpha syn and tau in mice resulted in pathological and behavioral phenotypes resembling Lewy body dementia (LBD). The findings showed that the overexpression of alpha syn in hTau and APP/PS1 mice, as well as the overexpression of tau in hThy1-alpha syn mice, did not recapitulate the behavioral and neuropathological phenotypes observed in LBD.
Article
Clinical Neurology
Amalia Perna, Kathleen S. Montine, Lon R. White, Thomas J. Montine, Brenna A. Cholerton
Summary: Neurodegenerative dementia arises from various abnormalities and the co-occurrence of multiple processes complicates identifying effective treatment targets. Current treatments mainly focus on symptoms and recently approved drugs for disease structures only have moderate benefit on symptom progression. Ongoing trials explore cognition enhancers, new drug combinations, less toxic prodrugs, and drugs targeting neuroinflammation or microbiome. A paradigm shift towards individualized and multimodal treatments is necessary to advance dementia therapeutics effectively.
Article
Medicine, General & Internal
Ping Guo, Weiming Gong, Yuanming Li, Lu Liu, Ran Yan, Yanjun Wang, Yanan Zhang, Zhongshang Yuan
Summary: This study investigates the genetic basis of Lewy body dementia (LBD) and the shared genetic etiology between LBD, Alzheimer's disease (AD), and Parkinson's disease (PD). The findings reveal genetic correlations between LBD and AD, LBD and PD, as well as AD and PD. Several significant loci and novel genetic associations for LBD are identified. Pathway enrichment analysis suggests the involvement of neurofibrillary tangle assembly in LBD. These findings provide insights into the genetic determinants and biological mechanisms of LBD and the relationships between LBD, AD, and PD.
Article
Health Care Sciences & Services
Pai-Yi Chiu, Po-Nien Hou, Guang-Uei Hung, Te-Chun Hsieh, Pak-Ki Chan, Chia-Hung Kao
Summary: This study evaluated the application of a machine learning-derived visual scale in diagnosing Lewy body disease and compared it with traditional semi-quantification methods. The results showed that the visual scale was effective in differentiating PD from NC, DLB from AD, and PDD from AD across different centers, with an acceptable correlation with traditional methods. Further research should focus on developing models using data pools from multiple centers to improve diagnostic accuracy.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Neurosciences
Yang Hyun Lee, Seun Jeon, Han Soo Yoo, Seok Jong Chung, Jin Ho Jung, Kyoungwon Baik, Young H. Sohn, Phil Hyu Lee, Mijin Yun, Alan C. Evans, Byoung Seok Ye
Summary: The study investigated the relationship among amyloid-beta deposition, cortical metabolism, and clinical diagnosis in AD and LBD patients. Results showed that AD and LBD patients commonly exhibited hypometabolism in specific brain regions. Combining clinical and metabolic evaluations may enhance the diagnostic accuracy of AD, LBD, and mixed disease cases.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Geriatrics & Gerontology
Amy N. Murray, Hannah L. Chandler, Thomas M. Lancaster
Summary: Preclinical models of Alzheimer's disease show that AD polygenic risk scores are linked to reduced MTL volumes before clinical onset. In a study of young participants, the AD-PRS was found to predict specific hippocampal subregions and demonstrate associations with whole hippocampal/amygdala volumes. This research provides novel insights into the relationship between AD-PRS and specific MTL subfields, potentially informing preclinical models of AD risk.
NEUROBIOLOGY OF AGING
(2021)
Article
Immunology
Stacie Z. Berg, Jonathan Berg
Summary: Melanin plays important roles in the immune system and its loss may contribute to various diseases. Melanin retains energy and its reduction could impair immune system defenses and plaque clearance. Regulating melanin levels may offer new avenues for treatment.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Neurosciences
Daijiro Yanagisawa, Nor Faeizah Ibrahim, Hiroyasu Taguchi, Shigehiro Morikawa, Tomoko Kato, Koichi Hirao, Nobuaki Shirai, Takayuki Sogabe, Ikuo Tooyama
JOURNAL OF NEUROSCIENCE RESEARCH
(2018)
Article
Multidisciplinary Sciences
Akihiko Shiino, Yen-wei Chen, Kenji Tanigaki, Atsushi Yamada, Piers Vigers, Toshiyuki Watanabe, Ikuo Tooyama, Ichiro Akiguchi
SCIENTIFIC REPORTS
(2017)
Article
Clinical Neurology
Takahiro Ito, Sachiko Tanaka-Mizuno, Narihito Iwashita, Ikuo Tooyama, Akihiko Shiino, Katsuyuki Miura, Sei Fukui
JOURNAL OF PAIN RESEARCH
(2017)
Article
Multidisciplinary Sciences
Yoshitaka Tamaki, Akemi Shodai, Toshifumi Morimura, Ryota Hikiami, Sumio Minamiyama, Takashi Ayaki, Ikuo Tooyama, Yoshiaki Furukawa, Ryosuke Takahashi, Makoto Urushitani
SCIENTIFIC REPORTS
(2018)
Article
Multidisciplinary Sciences
Faidruz Azura Jam, Yosuke Kadota, Anarmaa Mendsaikhan, Ikuo Tooyama, Masaki Mori
SCIENTIFIC REPORTS
(2018)
Article
Multidisciplinary Sciences
Daijiro Yanagisawa, Hamizah Shahirah Hamezah, Lina Wati Durani, Hiroyasu Taguchi, Ikuo Tooyama
Article
Cell Biology
Douglas G. Walker, Lih-Fen Lue, Thomas G. Beach, Ikuo Tooyama
Article
Biochemistry & Molecular Biology
Douglas G. Walker, Tiffany M. Tang, Anarmaa Mendsaikhan, Ikuo Tooyama, Geidy E. Serrano, Lucia I. Sue, Thomas G. Beach, Lih-Fen Lue
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Review
Biochemistry & Molecular Biology
Nur Zuliani Ramli, Mohamad Fairuz Yahaya, Ikuo Tooyama, Hanafi Ahmad Damanhuri
Review
Biochemistry & Molecular Biology
Haruka Tsubaki, Ikuo Tooyama, Douglas Gordon Walker
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Aslina Pahrudin Arrozi, Zulzikry Hafiz Abu Bakar, Hiroyasu Taguchi, Daijiro Yanagisawa, Ikuo Tooyama
Summary: Thioredoxin-interacting protein (TXNIP) is involved in disease-associated functions related to oxidative stress by inhibiting the activity of thioredoxin (TXN). The fluorine-19 magnetic resonance probe Shiga-Y5 (SY5) has therapeutic effects in an Alzheimer's disease mouse model, with its derivative Shiga-Y6 (SY6) acting as a TXNIP regulator. SY5 can be a potential therapeutic compound targeting the thioredoxin system in oxidative stress-related brain diseases.
Article
Biochemistry & Molecular Biology
Zulzikry Hafiz Abu Bakar, Jean-Pierre Bellier, Daijiro Yanagisawa, Tomoko Kato, Ken-ichi Mukaisho, Ikuo Tooyama
Summary: This study investigated the accumulation of FtMt and LC3 in the midbrain of patients with progressive supranuclear palsy (PSP) and proposed a hypothesis related to mitophagy processes. The findings suggested that FtMt may play a role in the progression of PSP.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Kazuyuki Takata, Hiroyuki Kimura, Daijiro Yanagisawa, Koki Harada, Kaneyasu Nishimura, Yoshihisa Kitamura, Shun Shimohama, Ikuo Tooyama
Summary: Research has found that in the early stages of Alzheimer's disease (AD), there is a decrease in choline signaling, including nicotinic acetylcholine receptors (nAChRs). Currently, there is limited understanding of AD pathophysiology, making it difficult to suppress the progression of the disease. Non-invasive diagnostic methods that can assess disease progression before the onset of symptoms are crucial, and incorporating the concept of neurotheranostics may be valuable for diagnosis and treatment.
Article
Biochemistry & Molecular Biology
Ayumi Uchino, Yumi Irie, Chihiro Tsukano, Taiji Kawase, Kenji Hirose, Yusuke Kageyama, Ikuo Tooyama, Ryo C. Yanagita, Kazuhiro Irie
Summary: Oligomers of the amyloid beta (A beta) protein play a critical role in the pathogenesis of Alzheimer's disease, but their structures and mechanisms are difficult to study due to their heterogeneity and instability. This study designed and synthesized trimer models with different linkers and found that some of them exhibited cytotoxicity and the ability to form protofibrillar species.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Cell Biology
Zulzikry Hafiz Abu Bakar, Jean-Pierre Bellier, Wan Zurinah Wan Ngah, Daijiro Yanagisawa, Ken-ichi Mukaisho, Ikuo Tooyama
Summary: The precision of colocalization analysis is improved by 3D technology, which is more accurate than 2D. However, generating a colocalization model may result in a complex model with numerous polygons. We developed a simplified 3D colocalization model of FtMt/LC3 and evaluated different simplification algorithms and quality assessment methods. Additionally, we found that using the x-ray shader can improve the visualization of colocalization.
