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
Radiology, Nuclear Medicine & Medical Imaging
Jing Wang, Chentao Jin, Jinyun Zhou, Rui Zhou, Mei Tian, Hyeon Jeong Lee, Hong Zhang
Summary: Alzheimer's disease is the most common dementia worldwide, and there is currently no exact etiology and effective treatment. Due to the complexity and heterogeneity of the disease, a range of biomarkers should be established to evaluate its severity and prognosis. Positron emission tomography is an effective imaging technique that allows for comprehensive observation and evaluation of Alzheimer's disease from diverse perspectives.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2023)
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.
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
Chemistry, Medicinal
Aya Ogata, Takashi Yamada, Saori Hattori, Hiroshi Ikenuma, Junichiro Abe, Mari Tada, Masanori Ichise, Masaaki Suzuki, Kengo Ito, Takashi Kato, Kazuma Amaike, Tsuyoshi Hirota, Akiyoshi Kakita, Kenichiro Itami, Yasuyuki Kimura
Summary: Positron emission tomography (PET) is a powerful imaging tool for early detection of Alzheimer's disease (AD) that has been developed to target beta-amyloid and tau protein aggregates. This study focuses on the development of a new PET ligand targeting protein kinase CK2, which is known to be altered in AD brains.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Clinical Neurology
Vijay K. Ramanan, Michael G. Heckman, Timothy G. Lesnick, Scott A. Przybelski, Elliot J. Cahn, Matthew L. Kosel, Melissa E. Murray, Michelle M. Mielke, Hugo Botha, Jonathan Graff-Radford, David T. Jones, Val J. Lowe, Mary M. Machulda, Clifford R. Jack, David S. Knopman, Ronald C. Petersen, Owen A. Ross, Prashanthi Vemuri
Summary: This study found that a polygenic risk score (PRS) based on tau PET can effectively capture tau deposition levels and genetic background influencing tau accumulation. It outperformed amyloid PET burden and APOE ε4 in capturing tau deposition. The tau PRS was also associated with cerebrospinal fluid phosphorylated tau levels and postmortem neurofibrillary tangle stage. Additionally, it showed an interaction with amyloid burden on cognitive decline.
ACTA NEUROPATHOLOGICA
(2022)
Article
Clinical Neurology
Cecilia Boccalini, Federica Ribaldi, Ines Hristovska, Annachiara Arnone, Debora Elisa Peretti, Linjing Mu, Max Scheffler, Daniela Perani, Giovanni B. Frisoni, Valentina Garibotto
Summary: Tau and neurodegeneration are strongly correlated with cognitive impairment in memory clinics, with tau showing the strongest association with cognitive decline over time. The use of tau PET imaging in memory clinics provides superior prognostic value compared to other neuroimaging modalities.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Zhi-Bo Wang, Lan Tan, Hui-Fu Wang, Shi-Dong Chen, Yan Fu, Pei-Yang Gao, Ya-Hui Ma, Yu Guo, Jia-Hui Hou, Dan-Dan Zhang, Jin-Tai Yu
Summary: This study aimed to assess the accuracy of biomarkers related to amyloid, tau, and neurodegeneration in predicting Alzheimer's disease (AD) neuropathology at different clinical stages. The results showed that amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) amyloid beta (Aβ)42/phosphorylated tau (p-tau)181 performed well in differentiating AD and predicting neuropathological changes in early and late clinical stages. However, CSF Aβ42 performed better in early clinical stage, while CSF p-tau181, CSF t-tau, and plasma p-tau181 performed better in late clinical stage.
ALZHEIMERS & DEMENTIA
(2023)
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
Hana Florian, Deli Wang, Steven E. Arnold, Merce Boada, Qi Guo, Ziyi Jin, Hui Zheng, Nahome Fisseha, Hari Varun Kalluri, Beatrice Rendenbach-Mueller, Kumar Budur, Michael Gold, Thomas Aware Investigators, Lealani Acosta, Thomas Ala, Sanka Amadoru, Jeffrey Apter, Steven Arnold, Merce Boada-Rovira, Anne Boerjesson-Hanson, Wendy Bond, Michael Borrie, Gabriella Bottini, Bruce Brew, Mark Brody, James Burke, Jeffrey Burns, Annalisa Chiari, Roger Clarnette, Sharon Cohen, Martin Farlow, Simon Fishman, Norman Foster, Kristian Frederiksen, Giovanni Frisoni, Nigel Gilchrist, Darren Gitelman, Ira Goodman, Marc Gordon, Neill Graff-Radford, Merja Hallikainen, Adrian Ivanoiu, Gregory Jicha, Michael Jonsson, Diana Kerwin, Dineke Koek, James Lah, Ayesha Lall, Elly Lee, Gabriel Leger, Peter Ljubenkov, Camillo Marra, Pablo Martinez-Lage, Joseph Masdeu, Scott McGinnis, Patrizia Mecocci, Philip Morris, Marshall Nash, Allison Perrin, Aimee Pierce, Robert Riesenberg, Juha Rinne, Raquel Sanchez Del Valle, Elio Scarpini, Paul Schulz, Ronald Schwartz, Amanda Smith, Bryan Spann, Sylvie Van Snick, Rik Vandenberghe, Cherian Verghese, Alberto Villarejo, Chuang-Kuo Wu
Summary: Tau accumulation in patients with Alzheimer's disease is closely related to cognitive decline. This study evaluated tilavonemab, an anti-tau monoclonal antibody, in treating patients with early Alzheimer's disease. The results showed that tilavonemab did not demonstrate efficacy in treating early Alzheimer's disease.
Review
Immunology
Jie Huang
Summary: This review discusses the current status and applications of molecule-based positron emission tomography (PET) imaging in neuroinflammation. Despite certain limitations, neuroinflammation PET imaging is considered a promising approach to understanding the pathophysiological process of Alzheimer's disease (AD) and mild cognitive impairment (MCI).
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Clinical Neurology
Alexis Moscoso, Michel J. Grothe, Nicholas J. Ashton, Thomas K. Karikari, Juan Lantero Rodriguez, Anniina Snellman, Marc Suarez-Calvet, Henrik Zetterberg, Kaj Blennow, Michael Scholl
Summary: Measurement of tau phosphorylated at threonine 181 (p-tau181) in blood plasma is proposed as a specific biomarker for Alzheimer's disease. Longitudinal study reveals that plasma p-tau181 increases before amyloid-beta markers reach abnormal levels, correlating with amyloid-beta pathology. Plasma p-tau181 also shows associations with widespread cortical tau aggregation and may be a useful diagnostic and screening tool for Alzheimer's disease.
Article
Neurosciences
Xi Chen, Kaitlin E. Cassady, Jenna N. Adams, Theresa M. Harrison, Suzanne L. Baker, William J. Jagust
Summary: Studies suggest that tau deposition begins in the anterolateral entorhinal cortex during normal aging and is facilitated by the presence of beta-amyloid, potentially marking the onset of Alzheimer's disease. Higher tau deposition in the anterior-temporal memory network is associated with faster memory decline, especially in individuals with beta-amyloid. When all three tau measures are considered, only tau in the anterior-temporal region significantly predicts memory decline.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Debora E. Peretti, Federica Ribaldi, Max Scheffler, Christian Chicherio, Giovanni B. Frisoni, Valentina Garibotto
Summary: The study assessed the relationship between ATN profiles defined through imaging and cognitive decline in a memory clinic cohort. The results showed that the AD-P group had the most significant cognitive decline over a period of 2 years, highlighting the value of amyloid and tau PET molecular imaging as prognostic imaging biomarkers in clinical practice.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2023)
Article
Neurosciences
Charles D. Chen, Maria Rosana Ponisio, Jordan A. Lang, Shaney Flores, Suzanne E. Schindler, Anne M. Fagan, John C. Morris, Tammie L. S. Benzinger
Summary: F-18-flortaucipir PET was approved by FDA for visualizing neurofibrillary tangles in the brains of patients with cognitive impairment. Visual interpretation was found to be consistent with SUVR and moderately consistent with CSF biomarkers. However, it could not predict the clinical assessment in some cases.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Chemistry, Medicinal
Brandon M. Taoka, Wen-Lian Wu, Jinsong Hao, Martin Dolmaski, Hongwu Wang, Dorthy Levorse, Peter Orth, Lynn A. Hyde, Brad Smith, Maria S. Michener, Matthew E. Kennedy, Eric M. Parker, Jared N. Cumming
Summary: This paper explores the structure-activity relationships of novel fluoroalkyl substituents at the C2 position of iminothiazine dioxide beta secretase inhibitors, highlighting the impact of reduced amidine basicity on Pgp, cell potency, and efficacy in preclinical in vivo animal models. The findings provide valuable insights into the mechanisms of action of these inhibitors.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
Mitchell H. Keylor, Anmol Gulati, Solomon D. Kattar, Rebecca E. Johnson, Ryan W. Chau, Kaila A. Margrey, Michael J. Ardolino, Cayetana Zarate, Kelsey E. Poremba, Vladimir Simov, Gregori J. Morriello, John J. Acton, Barbara Pio, Xin Yan, Rachel L. Palte, Spencer E. McMinn, Lisa Nogle, Charles A. Lesburg, Donovon Adpressa, Shishi Lin, Santhosh Neelamkavil, Ping Liu, Jing Su, Laxminarayan G. Hegde, Janice D. Woodhouse, Robert Faltus, Tina Xiong, Paul J. Ciaccio, Jennifer Piesvaux, Karin M. Otte, Harold B. Wood, Matthew E. Kennedy, David Jonathan Bennett, Erin F. DiMauro, Matthew J. Fell, Peter H. Fuller
Summary: The study successfully discovered brain-penetrant molecules with candidate-quality, high selectivity against the kinome, potency- and selectivity-enhancing design elements, and encouraging brain penetration in preclinical models.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Mathematical & Computational Biology
Kewei Chen, Xiaojuan Guo, Rong Pan, Chengjie Xiong, Danielle J. Harvey, Yinghua Chen, Li Yao, Yi Su, Eric M. Reiman
Summary: This study discusses the limitations of estimating sample size for randomized clinical trials based on available data from only two time points. Mathematical equations are derived to demonstrate the conditions under which data pairs with variable time intervals can be used for accurate sample size estimation. MRI-based hippocampal volume measurements and Monte Carlo simulations are used to illustrate the bias and variability of estimates. The results support the condition and show the potential for significant bias in sample size estimation using a subtractive approach.
STATISTICS IN MEDICINE
(2022)
Article
Biochemical Research Methods
Xiaojuan Guo, Kewei Chen, Yinghua Chen, Chengjie Xiong, Yi Su, Li Yao, Eric M. Reiman
Summary: A computational Monte-Carlo simulation (CMCS) was introduced to quantitatively determine the temporal ordering of abnormal age onsets (AAO) among various biomarkers for Alzheimer's disease (AD). The CMCS showed significant results in estimating the AAO ordering and provided important implications in advancing our understanding of AD.
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
(2022)
Article
Endocrinology & Metabolism
Tsubasa Tomoto, Aryan Verma, Kayla Kostroske, Takashi Tarumi, Neena R. Patel, Evan P. Pasha, Jonathan Riley, Cynthia D. Tinajero, Linda S. Hynan, Karen M. Rodrigue, Kristen M. Kennedy, Denise C. Park, Rong Zhang
Summary: This study found that one-year progressive, moderate-to-vigorous aerobic exercise training has positive effects on cerebral blood flow, central arterial stiffness, and cognitive performance. In cognitively normal older adults, aerobic exercise training increased cerebral blood flow, decreased carotid arterial stiffness and cerebrovascular resistance, and was associated with improved memory function.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2023)
Article
Neurosciences
Pavlina Mastrandreas, Andreas Arnold, Csaba Boglari, Dominique J-F De Quervain, Attila Stetak, Andreas Papassotiropoulos
Summary: Musashi RNA-binding proteins play a vital role in stem cell maintenance, tumorigenesis, and nervous system development. Inhibiting Musashi activity with a drug improved memory retention and reversed age-related memory decline.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Psychiatry
Sarah Wilker, Vanja Vukojevic, Anna Schneider, Anett Pfeiffer, Stefan Inerle, Markus Pauly, Thomas Elbert, Andreas Papassotiropoulos, Dominique de Quervain, Iris-Tatjana Kolassa
Summary: Epigenetic changes are associated with effective psychotherapy, and DNA methylation at the glucocorticoid receptor gene (NR3C1) is a potential biomarker for therapy success in treating Posttraumatic Stress Disorder (PTSD). This study found that methylation at CpG site cg25535999 was negatively associated with PTSD symptoms, and treatment responders showed an increase in this methylation after therapy. Lower methylation at cg25535999 before treatment predicted greater symptom improvement.
TRANSLATIONAL PSYCHIATRY
(2023)
Article
Clinical Neurology
M. Yuan, Kristen M. Kennedy
Summary: This study used geospatial tools and landmarks to assess environmental complexity and predict cognitive status. The results showed that street length, circuity, and points of interest were associated with dementia. Therefore, environmental complexity plays an important role in the development of Alzheimer's disease.
JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE
(2023)
Article
Clinical Neurology
Deming Jiang, Li Liu, Yu Kong, Zhongyun Chen, Pedro Rosa-Neto, Kewei Chen, Liankun Ren, Min Chu, Liyong Wu
Summary: Abnormal glymphatic function, especially in the anterior and middle regions of the brain, was found in patients with bvFTD. Regional glymphatic dysfunction may contribute to the pathogenesis of bvFTD.
ANNALS OF NEUROLOGY
(2023)
Review
Neurosciences
Bolong Wang, Yaojing Chen, Kewei Chen, Hui Lu, Zhanjun Zhang
Summary: Based on fluctuations in neighboring neurons, the blood oxygen level-dependent (BOLD) signal is a mesoscale measure of brain signals. Intraregional temporal features (IRTFs) of the BOLD signal, extracted from regional neural activities, are used to study the brain's functioning in localized brain areas. This literature review focuses on four types of IRTFs and their representative calculations, highlighting their relevance to cognitive processes. The spatial organization of these brain features reflects both structural constraints and hierarchical functional processing in the brain, and disruptions in this organization can shed light on age-related changes and neuropathology of brain diseases. Considering IRTFs in a brain-wide manner is crucial in understanding the brain's functional system.
HUMAN BRAIN MAPPING
(2023)
Article
Neurosciences
Stephan A. Muller, Merav D. Shmueli, Xiao Feng, Johanna Tushaus, Neele Schumacher, Ryan Clark, Brad E. Smith, An Chi, Stefan Rose-John, Matthew E. Kennedy, Stefan F. Lichtenthaler
Summary: In this study, the researchers identified SEZ6 and gp130/IL6ST as physiological substrates of BACE1 in non-human-primate cerebrospinal fluid. They also found a reduction of gp130 in human CSF from a clinical trial with a BACE inhibitor and in plasma of BACE1-deficient mice. These findings provide insights into the relationship between BACE1 and gp130 in neuronal signaling and survival.
MOLECULAR NEURODEGENERATION
(2023)
Article
Biochemistry & Molecular Biology
Leonora Szabo, Nadia Cummins, Paolo Paganetti, Alex Odermatt, Andreas Papassotiropoulos, Celeste Karch, Jurgen Gotz, Anne Eckert, Amandine Grimm
Summary: Abnormal tau protein disrupts the interaction between the endoplasmic reticulum (ER) and mitochondria, leading to impaired mitochondrial function and cholesterol metabolism. This study shows that abnormal tau loosens the association between ER and mitochondria, particularly through the VAPB-PTPIP51 pathway. Disruption of the ER-mitochondria interaction results in altered levels of mitochondrial cholesterol and pregnenolone, which can be restored by inhibiting GSK3 beta.
Article
Computer Science, Interdisciplinary Applications
Wenxiang Ding, Qiaoqiao Ding, Kewei Chen, Miao Zhang, Li Lv, David Dagan Feng, Lei Bi, Jinman Kim, Qiu Huang
Summary: Dynamic PET imaging provides more comprehensive physiological information than conventional static PET imaging. The proposed modified Logan reference plot model and self-supervised convolutional neural network improve noise performance and accurately estimate the distribution volume ratio in dynamic PET with a shortened scanning protocol. The method has the potential to add clinical value by providing both DVR and SUV simultaneously.
IEEE TRANSACTIONS ON MEDICAL IMAGING
(2023)
Article
Biotechnology & Applied Microbiology
Min Gu Kwak, Yi Su, Kewei Chen, David Weidman, Teresa Wu, Fleming Lure, Jing Li
Summary: Early diagnosis of Alzheimer's disease (AD) is important for treatment and prevention. This study proposes a self-supervised contrastive learning method, SMoCo, to accurately predict the conversion to AD in individuals with mild cognitive impairment using 3D amyloid-PET. The results demonstrate that SMoCo outperforms existing methods in classification performance.
BIOENGINEERING-BASEL
(2023)
Article
Computer Science, Cybernetics
Qunxi Dong, Zhigang Li, Weijia Liu, Kewei Chen, Yi Su, Jianfeng Wu, Richard J. Caselli, Eric M. Reiman, Yalin Wang, Jian Shen
Summary: This study aims to explore the relationship between plasma neurofilament light (NFL) levels and hippocampal morphometry using a proposed surface-based hippocampal morphometry system. Experimental results show that the system can effectively distinguish individuals with different plasma NFL levels and offers stronger statistical power compared to hippocampal volume measurement. This study is significant in revealing the pathology of Alzheimer's disease.
IEEE TRANSACTIONS ON COMPUTATIONAL SOCIAL SYSTEMS
(2023)
