Article
Medicine, General & Internal
Cecile Tissot, Joseph Therriault, Peter Kunach, Andrea L. Benedet, Tharick A. Pascoal, Nicholas J. Ashton, Thomas K. Karikari, Stijn Servaes, Firoza Z. Lussier, Mira Chamoun, Dana L. Tudorascu, Jenna Stevenson, Nesrine Rahmouni, Nina Margherita Poltronetti, Vanessa Pallen, Gleb Bezgin, Min Su Kang, Sulantha S. Mathotaarachchi, Yi-Ting Wang, Jaime Fernandez Arias, Pamela Cristina Lukasewicz Ferreira, Joao Pedro Ferrari-Souza, Eugeen Vanmechelen, Kaj Blennow, Henrik Zetterberg, Serge Gauthier, Pedro Rosa-Neto
Summary: This study investigated the agreement between [F-18]MK6240 tau-PET, plasma pTau181, and pTau231 in Alzheimer's disease. The findings suggest that these biomarkers reflect different stages of tau progression and can be useful in diagnosing and evaluating the disease stage.
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
Alexandra J. Weigand, Anne Maass, Graham L. Eglit, Mark W. Bondi
Summary: This study examined existing studies that derived tau PET cut-points and assessed the validity of different methods of tau PET thresholding. The findings showed variability among studies and provided recommendations for selecting cut-point derivations based on study goals.
ALZHEIMERS RESEARCH & THERAPY
(2022)
Article
Clinical Neurology
Eric E. Abrahamson, Julia K. Kofler, Carl R. Becker, Julie C. Price, Kathy L. Newell, Bernardino Ghetti, Jill R. Murrell, Catriona A. McLean, Oscar L. Lopez, Chester A. Mathis, William E. Klunk, Victor L. Villemagne, Milos D. Ikonomovic
Summary: In a post-mortem study, it has been found that the amyloid PET radioligand Pittsburgh compound B (PiB) interacts poorly with cotton wool plaques, which are common in familial Alzheimer's disease but rare in sporadic Alzheimer's disease. This limited interaction may lead to an underestimation of total amyloid burden in patients with familial Alzheimer's disease.
Article
Medicine, Research & Experimental
Aisling M. Chaney, Francisco R. Lopez-Picon, Sophie Serriere, Rui Wang, Daniela Bochicchio, Samuel D. Webb, Matthias Vandesquille, Michael K. Harte, Christina Georgiadou, Catherine Lawrence, Julie Busson, Johnny Vercouillie, Clovis Tauber, Frederic Buron, Sylvain Routier, Tristan Reekie, Anniina Snellman, Michael Kassiou, Johanna Rokka, Karen E. Davies, Juha O. Rinne, Dervis A. Salih, Frances A. Edwards, Llwyd D. Orton, Stephen R. Williams, Sylvie Chalon, Herve Boutin
Summary: The TgF344-AD rat model shows improved AD pathology modeling, including neuronal loss and Tau accumulation, with alterations in neuroinflammation and cholinergic receptors observed in vivo. This model can be useful for assessing early neurotransmission dysfunction and neuroinflammation in AD longitudinally, showing a potential for PET detection of Tau pathology.
Article
Radiology, Nuclear Medicine & Medical Imaging
Jiaying Lu, Zizhao Ju, Min Wang, Xun Sun, Chenhao Jia, Ling Li, Weiqi Bao, Huiwei Zhang, Fangyang Jiao, Huamei Lin, Tzu-Chen Yen, Ruixue Cui, Xiaoli Lan, Qianhua Zhao, Yihui Guan, Chuantao Zuo, Shanghai Memory Study SMS
Summary: This study evaluated the feasibility of quantifying F-18-florzolotau using a MRI-free PET template in AD patients. The results showed high agreement between the MRI-free and MRI-dependent methods in quantification and diagnostic performance. The robustness of the MRI-free approach was confirmed in the validation cohort.
EUROPEAN RADIOLOGY
(2023)
Article
Clinical Neurology
Hironobu Endo, Kenji Tagai, Maiko Ono, Yoko Ikoma, Asaka Oyama, Kiwamu Matsuoka, Naomi Kokubo, Kosei Hirata, Yasunori Sano, Masaki Oya, Hideki Matsumoto, Shin Kurose, Chie Seki, Hiroshi Shimizu, Akiyoshi Kakita, Keisuke Takahata, Hitoshi Shinotoh, Hitoshi Shimada, Takahiko Tokuda, Kazunori Kawamura, Ming-Rong Zhang, Kenichi Oishi, Susumu Mori, Yuhei Takado, Makoto Higuchi
Summary: This study aimed to establish tau PET pathology indices for characterizing PSP and AD using a machine learning approach. The results demonstrate the unbiased capability of our technology to identify topologies of 3R + 4R versus 4R tau deposits.
MOVEMENT DISORDERS
(2022)
Article
Clinical Neurology
William Charles Kreisl, Patrick J. Lao, Aubrey Johnson, Zeljko Tomljanovic, Julia Klein, Krista Polly, Benjamin Maas, Krystal K. Laing, Anthony G. Chesebro, Kay Igwe, Qolamreza R. Razlighi, Lawrence S. Honig, Xinyu Yan, Seonjoo Lee, Akiva Mintz, Jose A. Luchsinger, Yaakov Stern, D. P. Devanand, Adam M. Brickman
Summary: F-18-MK-6240 showed good correlation with CSF tau and p-tau levels, as well as age, cognition, and amyloid-based AD biomarkers. The study also found that F-18-MK-6240 binding patterns were associated with specific cognitive impairments in amyloid-positive participants, reflecting the progression of AD pathology.
ALZHEIMERS & DEMENTIA
(2022)
Article
Neurosciences
Yan Zhao, Jieming Zhang, Yue Chen, Jiehui Jiang
Summary: This study proposed a novel model based on deep learning radiomics to differentiate Alzheimer's disease patients, mild cognitive impairment patients, and normal control subjects. The model achieved the best classification performance compared to traditional models, and showed potential clinical value in discriminating AD, MCI, and NC.
Article
Clinical Neurology
J. Therriault, S. Gauthier, P. Rosa-Neto
Summary: Biomarkers have revolutionized the study and clinical diagnosis of Alzheimer's disease (AD), with tau pathology closely associated with neurodegeneration and clinical dysfunction. This makes tau-PET a useful tool for determining the severity of AD and monitoring its progression.
JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE
(2023)
Article
Clinical Neurology
Xin Wang, Iris Broce, Yuqi Qiu, Kacie D. Deters, Chun Chieh Fan, Anders M. Dale, Steven D. Edland, Sarah J. Banks
Summary: This study found that individuals in the high-risk group, identified based on polygenic hazard score (PHS), exhibited faster tau accumulation and cognitive decline in Alzheimer's disease clinical trials. Trials using the high-risk group as inclusion criteria would require a smaller sample size. Incorporating PHS as an inclusion criterion is a cost-effective and accessible method to identify potential participants for AD clinical trials.
ALZHEIMERS & DEMENTIA
(2023)
Article
Neurosciences
Natasha Krishnadas, Kun Huang, Stephanie A. Schultz, Vincent Dore, Pierrick Bourgeat, Anita M. Y. Goh, Fiona Lamb, Svetlana Bozinovski, Samantha C. Burnham, Joanne S. Robertson, Simon M. Laws, Paul Maruff, Colin L. Masters, Victor L. Villemagne, Christopher C. Rowe
Summary: This study confirms that tau distribution patterns can be visually identified using F-18-MK6240 PET, and these patterns are associated with differences in APOE epsilon 4 carriage, hippocampal volumes, and cognition.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Chemistry, Organic
Manuele Musolino, Ian N. Fleming, Lutz F. Schweiger, David O'Hagan, Sergio Dall'Angelo, Matteo Zanda
Summary: The synthesis of five radiotracers with different oxyamine spacers between the hypoxia-reactive 2-nitroimidazole moiety and the 5-[F-18]-fluorodeoxyribose prosthetic group was reported. Among them, tracer 15 d displayed superior uptake kinetics and similar selectivity for hypoxic cells compared to standard hypoxia tracers. Lipophilicity and structural rigidity significantly influenced the selectivity of the tracers towards hypoxic cells.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Clinical Neurology
Alexandra J. Weigand, Kelsey R. Thomas, Katherine J. Bangen, Graham M. L. Eglit, Lisa Delano-Wood, Paul E. Gilbert, Adam M. Brickman, Mark W. Bondi
Summary: The study revealed that APOE may interact with tau independently of Aβ, and elevated MTL tau levels have negative cognitive consequences in Aβ-negative ε4 carriers.
ALZHEIMERS & DEMENTIA
(2021)
Article
Clinical Neurology
Laura Nisenbaum, Robert Martone, Tianle Chen, Rajasimhan Rajagovindan, Gersham Dent, John Beaver, Carrie Rubel, Annie Racine, Ping He, Katie Harrison, Robert Dean, Manu Vandijck, Samantha Budd Haeberlein
Summary: This study assessed the use of cerebrospinal fluid (CSF) biomarkers as an alternative to positron emission tomography (PET) for confirming brain amyloid beta (A beta) pathology. The results showed a robust concordance between CSF biomarkers and amyloid PET, and the ratios of CSF biomarkers exhibited higher diagnostic accuracy for A beta pathology confirmation.
ALZHEIMERS & DEMENTIA
(2023)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)