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)
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)
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)
Review
Clinical Neurology
Jorge A. Trejo-Lopez, Anthony T. Yachnis, Stefan Prokop
Summary: Postmortem diagnosis remains central to Alzheimer's disease research, but advances in pathophysiology understanding and clinical diagnosis have shifted the perspective. In addition to the key pathological hallmarks, the diversity of accompanying pathological changes is gaining attention.
Article
Clinical Neurology
Binita Rajbanshi, Anuj Guruacharya, James W. Mandell, George S. Bloom
Summary: Tau phosphorylation at T217 increases as Alzheimer's disease progresses and is associated with diseased neurons. Extracellular tau oligomers can induce an increase in tau(pT217). Phosphorylation reduces tau's affinity for microtubules.
ALZHEIMERS & DEMENTIA
(2023)
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.
Article
Radiology, Nuclear Medicine & Medical Imaging
Justin P. Wright, Jason R. Goodman, Yin-Guo Lin, Brian P. Lieberman, Jennifer Clemens, Luis F. Gomez, Qianwa Liang, Adam T. Hoye, Michael J. Pontecorvo, Kelly A. Conway
Summary: The study aimed to evaluate the binding of [F-18]flortaucipir to MAO-A and MAO-B and its potential impact on PET interpretation. Results showed specific binding of flortaucipir to tau NFT-rich Alzheimer's disease tissue but minimal binding to MAO-A and MAO-B.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2022)
Article
Immunology
Xiao-ying Sun, Ling-jie Li, Quan-Xiu Dong, Jie Zhu, Ya-ru Huang, Sheng-jie Hou, Xiao-lin Yu, Rui-tian Liu
Summary: The study demonstrated that rutin could inhibit tau aggregation and tau oligomer-induced cytotoxicity, reduce the production of proinflammatory cytokines, protect neuronal morphology from toxic tau oligomers, and promote microglial uptake of extracellular tau oligomers. In a Tau-P301S mouse model, rutin also reduced pathological tau levels, regulated tau hyperphosphorylation, suppressed gliosis and neuroinflammation, prevented microglial synapse engulfment, and rescued synapse loss, resulting in a significant improvement of cognition. These findings suggest that rutin is a promising drug candidate for Alzheimer's disease treatment by targeting both tau and amyloid beta pathology.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Clinical Neurology
Jessica Camacho, Alberto Rabano, Paula Marazuela, Anna Bonaterra-Pastra, Garazi Serna, Teresa Moline, Santiago Ramon y Cajal, Elena Martinez-Saez, Mar Hernandez-Guillamon
Summary: Genome-wide association studies have identified several genes as genetic susceptibility loci for Alzheimer's disease, with CD2AP being one of them. CD2AP was found to be present in brain endothelial cells and neuronal inclusions in AD cases, showing association with tau pathology. The distribution of CD2AP in neurons was correlated with Braak neurofibrillary stage, suggesting a link between CD2AP expression and tau-related diseases.
Article
Clinical Neurology
David C. Hondius, Frank Koopmans, Conny Leistner, Debora Pita-Illobre, Regina M. Peferoen-Baert, Fenna Marbus, Iryna Paliukhovich, Ka Wan Li, Annemieke J. M. Rozemuller, Jeroen J. M. Hoozemans, August B. Smit
Summary: This study provides a comprehensive assessment of protein abundances in neurons with granulovacuolar degeneration (GVD) and those bearing neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) patients. The research revealed significant changes in protein composition in GVD and tangle-bearing neurons, with proteins related to protein folding, proteasomal function, endolysosomal pathway, and microtubule function being affected in GVD neurons. The study suggests that GVD is part of a pre-NFT stage in AD pathogenesis and may disrupt proteostasis and cellular homeostasis.
ACTA NEUROPATHOLOGICA
(2021)
Review
Biochemistry & Molecular Biology
Pasquale Picone, Tiziana Sanfilippo, Sonya Vasto, Sara Baldassano, Rossella Guggino, Domenico Nuzzo, Donatella Bulone, Pier Luigi San Biagio, Emanuela Muscolino, Roberto Monastero, Clelia Dispenza, Daniela Giacomazza
Summary: Alzheimer's disease is the most common neurodegenerative disorder in the elderly, characterized by senile plaques and neurofibrillary tangles. There is currently a lack of treatment options aside from symptomatic medications. This review presents research results on the use of peptides of different sizes for the treatment of Alzheimer's disease.
Article
Clinical Neurology
Tharick A. Pascoal, Andrea L. Benedet, Dana L. Tudorascu, Joseph Therriault, Sulantha Mathotaarachchi, Melissa Savard, Firoza Z. Lussier, Cecile Tissot, Mira Chamoun, Min Su Kang, Jenna Stevenson, Gassan Massarweh, Marie-Christine Guiot, Jean-Paul Soucy, Serge Gauthier, Pedro Rosa-Neto
Summary: It is crucial to track longitudinal tau tangles accumulation across the Alzheimer's disease spectrum to understand the natural history of tau pathology. The novel subnanomolar affinity tau tracer F-18-MK-6240 demonstrated the ability to detect tau accumulation in asymptomatic and symptomatic individuals. The study found different patterns of tau accumulation in early vs. late Braak stages, with implications for diagnosis and treatment of Alzheimer's disease.
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
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
Kanta Tanaka, Masatoshi Koga, Mayumi Fukuda-Doi, Adnan Qureshi, Haruko Yamamoto, Kaori Miwa, Masafumi Ihara, Kazunori Toyoda
Summary: This study used group-based trajectory modeling to analyze blood pressure changes in patients with acute intracerebral hemorrhage receiving antihypertensive treatment, and found that different blood pressure trajectories were associated with different outcomes. Specifically, the high-to-low SBP group showed increased risks of death or disability and acute kidney injury.
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.
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.
