Article
Radiology, Nuclear Medicine & Medical Imaging
Elizabeth C. Mormino, Tyler N. Toueg, Carmen Azevedo, Jessica B. Castillo, Wanjia Guo, Ayesha Nadiadwala, Nicole K. Corso, Jacob N. Hall, Audrey Fan, Alexandra N. Trelle, Marc B. Harrison, Madison P. Hunt, Sharon J. Sha, Gayle Deutsch, Michelle James, Carolyn A. Fredericks, Mary Ellen Koran, Michael Zeineh, Kathleen Poston, Michael D. Greicius, Mehdi Khalighi, Guido A. Davidzon, Bin Shen, Greg Zaharchuk, Anthony D. Wagner, Frederick T. Chin
Summary: In vivo measurements using (18)F-PI-2620 PET scans revealed significant differences in brain regions associated with Alzheimer's disease across different stages of the disease. This indicates the potential of (18)F-PI-2620 as a tool for visualizing tau aggregations in AD.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2021)
Article
Neurosciences
Barbara E. Stopschinski, Kelly Del Tredici, Sandi-Jo Estill-Terpack, Estifanos Ghebremdehin, Fang F. Yu, Heiko Braak, Marc I. Diamond
Summary: Tauopathies are neurodegenerative diseases characterized by the accumulation of tau aggregates in the brain. A study on sporadic Alzheimer's disease (AD) revealed that tau seeding assays can detect pathology in regions not identified by traditional staining methods like AT8, shedding light on previously unrecognized sites of tau deposition. The variation in seeding sites among individuals may contribute to differences in the clinical presentation and progression of AD.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Medicine, Research & Experimental
Kaixiang Zhou, Fan Yang, Yuying Li, Yimin Chen, Xiaojun Zhang, Jinming Zhang, Junfeng Wang, Jiapei Dai, Lisheng Cai, Mengchao Cui
Summary: This study evaluated three pairs of optically pure F-18-labeled 2-phenylquinoxaline derivatives as potential Tau imaging agents for AD diagnosis, showing high selectivity and affinity for Tau tangles over A beta. The PET probes (R)-[F-18]5 and (S)-[F-18]16 demonstrated promising brain penetration, kinetics, and stability, making them suitable candidates for Tau tangle imaging.
MOLECULAR PHARMACEUTICS
(2021)
Article
Multidisciplinary Sciences
Georg Meisl, Eric Hidari, Kieren Allinson, Timothy Rittman, Sarah L. DeVos, Justin S. Sanchez, Catherine K. Xu, Karen E. Duff, Keith A. Johnson, James B. Rowe, Bradley T. Hyman, Tuomas P. J. Knowles, David Klenerman
Summary: The study reveals that limiting local replication may constitute the most promising strategy to control tau accumulation in Alzheimer's disease, starting from Braak stage III.
Article
Clinical Neurology
Shama D. Karanth, Yuriko Katsumata, Peter T. Nelson, David W. Fardo, Jaclyn K. McDowell, Frederick A. Schmitt, Richard J. Kryscio, Steven R. Browning, Dejana Braithwaite, Susanne M. Arnold, Erin L. Abner
Summary: This study investigated the association between cancer diagnosis and neuropathological and cognitive features of dementia. The findings showed that cancer diagnosis was associated with a lower burden of Alzheimer's disease pathology and less cognitive impairment.
Article
Clinical Neurology
Paul A. Yushkevich, Monica Munoz Lopez, Maria Mercedes Iniguez de Onzono Martin, Ranjit Ittyerah, Sydney Lim, Sadhana Ravikumar, Madigan L. Bedard, Stephen Pickup, Weixia Liu, Jiancong Wang, Ling Yu Hung, Jade Lasserve, Nicolas Vergnet, Long Xie, Mengjin Dong, Salena Cui, Lauren McCollum, John L. Robinson, Theresa Schuck, Robin de Flores, Murray Grossman, M. Dylan Tisdall, Karthik Prabhakaran, Gabor Mizsei, Sandhitsu R. Das, Emilio Artacho-Perula, Mari'a Del Mar Arroyo Jimenez, Mari'a Pilar Marcos Raba, Francisco Javier Molina Romero, Sandra Cebada Sanchez, Jose Carlos Delgado Gonzalez, Carlos De la Rosa-Prieto, Marta Corcoles Parada, Edward B. Lee, John Q. Trojanowski, Daniel T. Ohm, Laura E. M. Wisse, David A. Wolk, David J. Irwin, Ricardo Insausti
Summary: This study utilized ex vivo MRI and dense serial histological imaging to construct three-dimensional quantitative maps of neurofibrillary tangle burden in the medial temporal lobe, revealing significant variation along different anatomical regions. The findings provide valuable insights into the distribution of this neurodegenerative pathology and may support the development and validation of neuroimaging biomarkers.
Article
Neurosciences
Sadhana Ravikumar, Laura E. M. Wisse, Sydney Lim, Ranjit Ittyerah, Long Xie, Madigan L. Bedard, Sandhitsu R. Das, Edward B. Lee, M. Dylan Tisdall, Karthik Prabhakaran, Jacqueline Lane, John A. Detre, Gabor Mizsei, John Q. Trojanowski, John L. Robinson, Theresa Schuck, Murray Grossman, Emilio Artacho-Perula, Maria Mercedes Iniguez de Onzono Martin, Maria Del Mar Arroyo Jimenez, Monica Munoz, Francisco Javier Molina Romero, Maria Del Pilar Marcos Rabal, Sandra Cebada Sanchez, Jose Carlos Delgado Gonzalez, Carlos de la Rosa Prieto, Marta Corcoles Parada, David J. Irwin, David A. Wolk, Ricardo Insausti, Paul A. Yushkevich
Summary: The study revealed a close association between tau neurofibrillary tangle pathology and neurodegeneration in the medial temporal lobe. Significant correlations were found between regional thickness in the entorhinal cortex and stratum radiatum lacunosum moleculare and tau pathology severity, especially in cases with low levels of TDP-43 pathology.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Andrea Gonzalez, Sandeep Kumar Singh, Macarena Churruca, Ricardo B. Maccioni
Summary: Alzheimer's disease is a neurodegenerative disease characterized by progressive cognitive impairment, apathy, and neuropsychiatric disorders. The main pathological features are tau oligomers and Aβ plaques. Protein kinases and phosphatases play a role in the hyperphosphorylation of tau and its self-assembly.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Medicine, Research & Experimental
Mehdi Sanati, Samaneh Aminyavari, Amir R. Afshari, Amirhossein Sahebkar
Summary: Alzheimer's disease (AD) is a type of dementia characterized by memory decline and cognition impairment. There are similarities between AD and noninsulin-dependent diabetes mellitus (NIDDM), which suggests that metformin, a hypoglycemic agent, could be used as an alternative therapy for AD. Preclinical studies have shown that metformin can improve cognition and memory impairment in AD models through various mechanisms.
Review
Chemistry, Medicinal
Caitlin V. M. L. Jie, Valerie Treyer, Roger Schibli, Linjing Mu
Summary: Tauvid, approved by the FDA in 2020 for PET imaging in AD patients, is a significant advancement in the field of AD research. This review summarizes the production, quality control, clinical application, pharmacology, and limitations of Tauvid, while also providing an overview of second-generation tau PET tracers.
Review
Biotechnology & Applied Microbiology
Sai Sreenivasamurthy, Mahek Laul, Nan Zhao, Tiffany Kim, Donghui Zhu
Summary: Alzheimer's disease is a progressive neurodegenerative disease associated with aging. Two-dimensional cell culture and animal models have contributed to our understanding of the disease mechanism, but they cannot fully capture the complexity of human brain tissue. The emergence of three-dimensional cerebral organoid models offers a more accurate representation of human brain tissue.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
Article
Chemistry, Multidisciplinary
Truc T. Huynh, Yujue Wang, Karna Terpstra, Hong-Jun Cho, Liviu M. Mirica, Buck E. Rogers
Summary: This study introduces novel bifunctional chelators that can effectively bind with amyloid fibrosis and show promising potential for detecting and managing cerebral amyloid angiopathy.
Article
Clinical Neurology
Yalun Zhang, Yi Zhang, Yahyah Aman, Cheung Toa Ng, Wing-Hin Chau, Zhigang Zhang, Ming Yue, Christopher Bohm, Yizhen Jia, Siwen Li, Qiuju Yuan, Jennifer Griffin, Kin Chiu, Dana S. M. Wong, Binbin Wang, Dongyan Jin, Ekaterina Rogaeva, Paul E. Fraser, Evandro F. Fang, Peter St George-Hyslop, You-Qiang Song
Summary: Research has shown that the transcription factor PAX6 is increased in Alzheimer's disease, playing a key role in the hyperphosphorylation of tau protein induced by amyloid-beta. Downregulation of PAX6 can protect against amyloid-beta-induced neuronal death. This study provides novel potential targets for pharmaceutical intervention by modulating signaling pathways involving CDK/pRB/E2F1.
Review
Biochemistry & Molecular Biology
Zohreh Mohammadi, Hadi Alizadeh, Janos Marton, Paul Cumming
Summary: Hyperphosphorylated tau aggregates are characteristic features of Alzheimer's disease (AD). The development of molecular imaging of tau by positron emission tomography (PET) started with [F-18]FDDNP, which had off-target binding to tau and obtained regional specificity through the distribution of amyloid beta and tau in AD brains. Several tau PET tracers have been developed, with F-18-flortaucipir being the first approved by the FDA. These tracers differ in selectivity, off-target binding, and uptake in white matter. In this review, the binding properties of the tracers in vitro and their effectiveness in discriminating between AD patients and healthy controls were compared. The available tracers showed good discrimination, with higher effectiveness in more severe AD patients.
Article
Clinical Neurology
Sanaz Arezoumandan, Sharon X. Xie, Katheryn A. Q. Cousins, Dawn J. Mechanic-Hamilton, Claire S. Peterson, Camille Y. Huang, Daniel T. Ohm, Ranjit Ittyerah, Corey T. McMillan, David A. Wolk, Paul Yushkevich, John Q. Trojanowski, Edward B. Lee, Murray Grossman, Jeffrey S. Phillips, David J. Irwin
Summary: Alzheimer's disease can present with different clinical variants due to heterogeneous neuropathologic changes. This study investigated the distribution and burden of tau pathologies in different brain regions among amnestic and non-amnestic phenotypic variants of Alzheimer's disease. The results showed that there were differences in the distribution and burden of tau pathologies between the two groups, suggesting that the neuronal susceptibility to tau-mediated neurodegeneration may influence the clinical expression of Alzheimer's disease.
ACTA NEUROPATHOLOGICA
(2022)
Article
Clinical Neurology
Kaori Miwa, Masatoshi Koga, Manabu Inoue, Sohei Yoshimura, Makoto Sasaki, Yusuke Yakushiji, Mayumi Fukuda-Doi, Yasushi Okada, Taizen Nakase, Masafumi Ihara, Yoshinari Nagakane, Shunya Takizawa, Koko Asakura, Junya Aoki, Kazumi Kimura, Haruko Yamamoto, Kazunori Toyoda
Summary: New cerebral microbleeds developed within 36 h in 11% of patients after intravenous thrombolysis, and they were significantly associated with mixed-distribution and >= 5 cerebral microbleeds.
INTERNATIONAL JOURNAL OF STROKE
(2022)
Review
Clinical Neurology
Kazunori Toyoda, Sohei Yoshimura, Mayumi Fukuda-Doi, Adnan Qureshi, Renee' Hebert Martin, Yuko Y. Palesch, Masafumi Ihara, Jose Suarez, Yasushi Okada, Chung Y. Hsu, Ryo Itabashi, Yongjun Wang, Hiroshi Yamagami, Thorsten Steiner, Nobuyuki Sakai, Byung-Woo Yoon, Manabu Inoue, Kazuo Minematsu, Haruko Yamamoto, Masatoshi Koga
Summary: The study showed that rapid lowering of systolic blood pressure by continuous administration of intravenous nicardipine in patients with hyperacute intracerebral hemorrhage was associated with lower risks of hematoma expansion and 90-day death or disability, without increasing serious adverse events.
INTERNATIONAL JOURNAL OF STROKE
(2022)
Editorial Material
Cardiac & Cardiovascular Systems
Masafumi Ihara
CIRCULATION RESEARCH
(2022)
News Item
Clinical Neurology
Masafumi Ihara, Yumi Yamamoto
Summary: Single-cell transcriptomic analyses of human brain microvessels have identified transcriptomic signatures and transcriptional changes in the cerebrovasculature in neurodegenerative diseases, which could significantly contribute to our understanding of brain health and disease.
NATURE REVIEWS NEUROLOGY
(2022)
Article
Clinical Neurology
Junpei Koge, Kanta Tanaka, Takeshi Yoshimoto, Masayuki Shiozawa, Yuji Kushi, Tsuyoshi Ohta, Tetsu Satow, Hiroharu Kataoka, Masafumi Ihara, Masatoshi Koga, Noriko Isobe, Kazunori Toyoda
Summary: Tortuosity of the internal carotid artery (ICA) affects the outcomes of mechanical thrombectomy, with lower first pass effect rate and higher risk of intracranial hemorrhage in patients with greater tortuosity.
Article
Clinical Neurology
Takeshi Yoshimoto, Kazunori Toyoda, Masafumi Ihara, Hiroshi Inoue, Takeshi Yamashita, Shinya Suzuki, Masaharu Akao, Hirotsugu Atarashi, Takanori Ikeda, Ken Okumura, Yukihiro Koretsune, Wataru Shimizu, Hiroyuki Tsutsui, Atsushi Hirayama, Masahiro Yasaka, Hirofumi Maruyama, Satoshi Teramukai, Tetsuya Kimura, Yoshiyuki Morishima, Atsushi Takita, Takenori Yamaguchi
Summary: The history of stroke/TIA in elderly patients increases the risk of stroke, bleeding, and death. Among patients with prior ischemic stroke/TIA, taking direct oral anticoagulants reduces the risk of bleeding events.
Article
Cardiac & Cardiovascular Systems
Takashi Okada, Takeshi Yoshimoto, Shinichi Wada, Sohei Yoshimura, Tetsuya Chiba, Shuhei Egashira, Shunsuke Kimura, Masayuki Shiozawa, Manabu Inoue, Masafumi Ihara, Kazunori Toyoda, Hiroshi Takashima, Masatoshi Koga
Summary: This study aimed to evaluate the safety of treatment with alteplase at 0.6 mg/kg within 24 hours for patients on direct oral anticoagulants (DOACs) before ischemic stroke onset. The results suggest that intravenous thrombolysis can be safely performed for DOACs patients following the recommendations of the guidelines.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Review
Clinical Neurology
Yumi Yamamoto, Yi-Chu Liao, Yi-Chung Lee, Masafumi Ihara, Jay Chol Choi
Summary: CADASIL is the most common monogenic disorder of the cerebral small blood vessels, caused by mutations in the NOTCH3 gene. Recent large-scale genomic studies have revealed a high prevalence of pathogenic NOTCH3 variants among the general population, with the highest risk being among Asians. The exact pathogenesis of CADASIL remains unclear, despite various laboratory and clinical observations being made.
JOURNAL OF CLINICAL NEUROLOGY
(2023)
Article
Nutrition & Dietetics
Takayuki Inoue, Bin Fu, Miwako Nishio, Miyako Tanaka, Hisashi Kato, Masashi Tanaka, Michiko Itoh, Hajime Yamakage, Kozue Ochi, Ayaka Ito, Yukihiro Shiraki, Satoshi Saito, Masafumi Ihara, Hideo Nishimura, Atsuhiko Kawamoto, Shian Inoue, Kumiko Saeki, Atsushi Enomoto, Takayoshi Suganami, Noriko Satoh-Asahara
Summary: The molecular pathogenesis of nonalcoholic steatohepatitis (NASH) involves metabolic stress and inflammatory stimuli. In this study, we found that Taxifolin treatment effectively prevented hepatic steatosis, chronic inflammation, and liver fibrosis in a NASH murine model. Taxifolin inhibited lipid accumulation in hepatocytes and increased brown adipose tissue activity. Furthermore, Taxifolin treatment after NASH development could prevent the development of liver tumors. These findings indicate the pleiotropic effects of Taxifolin for NASH treatment.
Editorial Material
Biochemistry & Molecular Biology
Hiroyuki Ishiyama, Masafumi Ihara
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Nutrition & Dietetics
Masayo Iwasa, Hisashi Kato, Kaori Iwashita, Hajime Yamakage, Sayaka Kato, Satoshi Saito, Masafumi Ihara, Hideo Nishimura, Atsuhiko Kawamoto, Takayoshi Suganami, Masashi Tanaka, Noriko Satoh-Asahara
Summary: This study found that a high-glucose environment can increase intracellular reactive oxygen species (ROS) levels and trigger inflammation in microglial cells, leading to cognitive impairment in diabetes. However, taxifolin, a natural flavonoid, has been shown to reduce ROS levels and inhibit the activation of the TXNIP-NLRP3 axis, thereby suppressing inflammation and preventing cognitive impairment in diabetes.
Letter
Clinical Neurology
Yoshito Arakaki, Takeshi Yoshimoto, Hiroyuki Ishiyama, Tomotaka Tanaka, Yorito Hattori, Masafumi Ihara
JOURNAL OF MOVEMENT DISORDERS
(2023)
Article
Health Care Sciences & Services
Satoshi Suda, Takehiro Katano, Kazuo Kitagawa, Yasuyuki Iguchi, Shigeru Fujimoto, Kenjiro Ono, Osamu Kano, Hidehiro Takekawa, Masatoshi Koga, Masafumi Ihara, Masafumi Morimoto, Hiroshi Yamagami, Tadashi Terasaki, Keiji Yamaguchi, Seiji Okubo, Yuji Ueno, Nobuyuki Ohara, Yuki Kamiya, Masataka Takeuchi, Yukako Yazawa, Yuka Terasawa, Ryosuke Doijiri, Yoshifumi Tsuboi, Kazutaka Sonoda, Koichi Nomura, Takashi Shimoyama, Akihito Kutsuna, Kazumi Kimura
Summary: This study aims to evaluate the proportion, timing, and characteristics of atrial fibrillation (AF) detection in patients with cryptogenic stroke (CS) using insertable cardiac monitors (ICMs). It also aims to compare patient characteristics and outcomes between those with AF and those without AF. The study has started and the main results are expected to be published in 2023. The findings of this study will contribute to the identification of AF markers and the development of a new and improved screening algorithm for AF detection, as well as aiding in the selection of patients for ICM implantation and the development of diagnostic criteria for CS in Japan.
JMIR RESEARCH PROTOCOLS
(2023)
Article
Clinical Neurology
Takehito Kuroda, Tomotaka Tanaka, Soichiro Abe, Manabu Inoue, Yoshiaki Morita, Takuto Mukaida, Takamasa Iwai, Masafumi Ihara
EPILEPTIC DISORDERS
(2023)
Article
Medicine, General & Internal
Satoshi Suda, Chikako Nito, Masafumi Ihara, Yasuyuki Iguchi, Takao Urabe, Yuji Matsumaru, Nobuyuki Sakai, Kazumi Kimura
Summary: This study aims to evaluate the safety and efficacy of a novel cell-based therapy product called JTR-161 for patients with acute ischemic stroke. The study will be conducted in Japan and will use a randomized, double-blind, placebo-controlled design. The results of the study will be disseminated through informed consent forms and peer-reviewed publication.