Article
Clinical Neurology
Clifford R. Jack Jr, Heather J. Wiste, Alicia Algeciras-Schimnich, Dan J. Figdore, Christopher G. Schwarz, Val J. Lowe, Vijay K. Ramanan, Prashanthi Vemuri, Michelle M. Mielke, David S. Knopman, Jonathan Graff-Radford, Bradley F. Boeve, Kejal Kantarci, Petrice M. Cogswell, Matthew L. Senjem, Jeffrey L. Gunter, Terry M. Therneau, Ronald C. Petersen
Summary: Staging the severity of Alzheimer's disease pathology is important for therapeutic trials and clinical prognosis. Biomarkers such as amyloid and tau PET can be used for disease staging, but plasma biomarkers would be more practical.
Article
Clinical Neurology
Emma M. Coomans, Jori Tomassen, Rik Ossenkoppele, Sandeep S. Golla, Marijke den Hollander, Lyduine E. Collij, Emma Weltings, Sophie M. van der Landen, Emma E. Wolters, Albert D. Windhorst, Frederik Barkhof, Eco J. C. de Geus, Philip Scheltens, Pieter Jelle Visser, Bart N. M. van Berckel, Anouk den Braber
Summary: Coomans et al. found substantial similarities in tau load and spatial distribution among identical twins, indicating a significant role of genetic factors in tau pathology. However, differences between twin pairs suggest the influence of environmental factors in tau accumulation. This study provides insights into factors associated with tau pathology and may be important for preventive strategies against Alzheimer's disease.
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.
Article
Medicine, Research & Experimental
Rik Ossenkoppele, Juhan Reimand, Ruben Smith, Antoine Leuzy, Olof Strandberg, Sebastian Palmqvist, Erik Stomrud, Henrik Zetterberg, Philip Scheltens, Jeffrey L. Dage, Femke Bouwman, Kaj Blennow, Niklas Mattsson-Carlgren, Shorena Janelidze, Oskar Hansson
Summary: The study found that biomarkers of tau pathology may be differently associated with various factors related to Alzheimer's disease. CSF and plasma p-tau181 and p-tau217 levels are more closely linked to early markers of the disease, while tau-PET shows stronger associations with cognitive and neurodegenerative markers of disease progression.
EMBO MOLECULAR MEDICINE
(2021)
Article
Clinical Neurology
Jeremy A. Tanner, Leonardo Iaccarino, Lauren Edwards, Breton M. Asken, Maria L. Gorno-Tempini, Joel H. Kramer, Julie Pham, David C. Perry, Katherine Possin, Maura Malpetti, Taylor Mellinger, Bruce L. Miller, Zachary Miller, Nidhi S. Mundada, Howard J. Rosen, David N. Soleimani-Meigooni, Amelia Strom, Renaud La Joie, Gil D. Rabinovici
Summary: Tanner et al. studied the correlation between cognition and PET biomarkers in early-onset and late-onset Alzheimer's disease. They found that tau and neurodegeneration were similarly associated with cognition in both age groups, suggesting tau PET as a biomarker that captures clinical severity and molecular pathology across ages. This research sheds light on the differences between early-onset and late-onset Alzheimer's disease and highlights the importance of tau PET as a tool for understanding the disease.
Review
Chemistry, Multidisciplinary
Yuying Li, Tianqing Liu, Mengchao Cui
Summary: This review summarizes the latest development of Tau tracers and analyzes their chemical structures and biological properties. The limitations of current tracers and considerations for the development of new tracers are also discussed.
CHINESE CHEMICAL LETTERS
(2022)
Review
Biochemistry & Molecular Biology
Ashwini Prem Kumar, Nivedita Singh, Deepak Nair, Antony Justin
Summary: Advancements in brain imaging techniques, especially with Positron emission tomography (PET), have become a significant tool in detecting Alzheimer's disease progression. The focus on investigational PET tracers targeting neurofibrillary tau aggregates found typically in AD is highlighted in this review. The discussion of the importance of several PET radiotracers and challenges in PET imaging is also emphasized.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Clinical Neurology
Edmond Teng, Paul T. Manser, Sandra Sanabria Bohorquez, Kristin R. Wildsmith, Karen Pickthorn, Suzanne L. Baker, Michael Ward, Geoffrey A. Kerchner, Robby M. Weimer
Summary: This study evaluated the relationship between tau PET imaging and subsequent cognitive decline in Alzheimer's disease. The results indicated that higher baseline tau PET signal was associated with faster rates of cognitive decline. Tau PET imaging may be useful for identifying AD patients at risk for more rapid cognitive decline.
ALZHEIMERS RESEARCH & THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Michael Rullmann, Matthias Brendel, Matthias L. Schroeter, Dorothee Saur, Johannes Levin, Robert G. Perneczky, Solveig Tiepolt, Marianne Patt, Andre Mueller, Victor L. Villemagne, Joseph Classen, Andrew W. Stephens, Osama Sabri, Henryk Barthel
Summary: This study utilized the F-18-PI-2620 tracer and PET imaging to perform Tau Braak staging in patients with AD, and found that PET positivity closely followed the Braak staging scheme, allowing for the categorization of most cases into the six-stage hierarchical Braak model.
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
Clinical Neurology
Petrice M. Cogswell, Emily S. Lundt, Terry M. Therneau, Heather J. Wiste, Jonathan Graff-Radford, Alicia Algeciras-Schimnich, Val J. Lowe, Michelle M. Mielke, Christopher G. Schwarz, Matthew L. Senjem, Jeffrey L. Gunter, David S. Knopman, Prashanthi Vemuri, Ronald C. Petersen, Clifford R. Jack Jr
Summary: The temporal co-evolution of plasma and PET Alzheimer's disease biomarkers was evaluated in this study. Plasma p-tau progression was strongly associated with A beta PET and GFAP progression. GFAP became abnormal first, followed by A beta PET, plasma p-tau, and tau PET.
ALZHEIMERS & DEMENTIA
(2023)
Article
Neurosciences
Theresa M. Harrison, Tyler J. Ward, Alice Murphy, Suzanne L. Baker, Pablo A. Dominguez, Robert Koeppe, Prashanthi Vemuri, Samuel N. Lockhart, Youngkyoo Jung, Danielle J. Harvey, Laura Lovato, Arthur W. Toga, Joseph Masdeu, Hwamee Oh, Darren R. Gitelman, Neelum Aggarwal, Heather M. Snyder, Laura D. Baker, Charles DeCarli, William J. Jagust, Susan M. Landau, US POINTER Study Grp
Summary: The POINTER Imaging ancillary study is evaluating the effect of risk reduction strategies in older adults at increased risk for cognitive decline. Different methods for minimizing off-target signal (OTS) effects did not significantly improve the performance metrics, as OTS contamination cancels out in the data.
Review
Clinical Neurology
Ariane G. Bollack, Hugh G. E. Pemberton, Lyduine E. Collij, Pawel M. Markiewicz, David M. Cash, Gill Farrar, Frederik Barkhof
Summary: This review summarizes the current design and methodologies of longitudinal PET studies, utilizing positron emission tomography to quantify amyloid and tau pathology. The intrinsic variability of AD protein load over time and technical factors contributing to PET measurement uncertainty are detailed. Suggestions for mitigating these factors, including leveraging shared information between serial scans, are provided.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Deborah N. Schoonhoven, Emma M. Coomans, Ana P. Millan, Anne M. van Nifterick, Denise Visser, Rik Ossenkoppele, Hayel Tuncel, Wiesje M. van der Flier, Sandeep S. Golla, Philip Scheltens, Arjan Hillebrand, Bart N. M. van Berckel, Cornelis J. Stam, Alida A. Gouw
Summary: Recent studies suggest that tau proteins spread through the brain in Alzheimer's disease (AD) following neuronal connections. Functional connectivity plays an important role in tau propagation, followed by structural connections and simple diffusion. Understanding the spreading pathways of tau could aid in identifying targets for future therapy.
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
Biochemistry & Molecular Biology
Ryuichi Harada, Yuki Shimizu, Yiqing Du, Yoichi Ishikawa, Ren Iwata, Yukitsuka Kudo, Kazuhiko Yanai, Nobuyuki Okamura, Shozo Furumoto
Summary: In this study, the effect of the chirality of [F-18]SMBT-1 on its performance as a tracer was investigated. (S)-[F-18]6 showed higher binding affinity and selectivity for MAO-B compared to (R)-[F-18]6. Additionally, (S)-[F-18]6 exhibited better pharmacokinetic and metabolic properties. These findings suggest that (S)-[F-18]6 is a promising candidate for in vivo imaging of MAO-B.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Neurosciences
Takashi Nihashi, Keita Sakurai, Takashi Kato, Kaori Iwata, Yasuyuki Kimura, Hiroshi Ikenuma, Akiko Yamaoka, Akinori Takeda, Yutaka Arahata, Yukihiko Washimi, Keisuke Suzuki, Masahiko Bundo, Takashi Sakurai, Nobuyuki Okamura, Kazuhiko Yanai, Kengo Ito, Akinori Nakamura
Summary: Using the F-18-THK5351 tracer, the study investigated the changes in accumulation patterns in individuals along the Alzheimer's disease continuum. The results showed an increase in F-18-THK5351 accumulation with disease progression, suggesting its potential as a tool for visualizing the severity of Alzheimer's disease.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Victor L. Villemagne, Ryuichi Harada, Vincent Dore, Shozo Furumoto, Rachel Mulligan, Yukitsuka Kudo, Samantha Burnham, Natasha Krishnadas, Svetlana Bozinovski, Kun Huang, Brian J. Lopresti, Kazuhiko Yanai, Christopher C. Rowe, Nobuyuki Okamura
Summary: The study found that 18F-SMBT-1 is a highly selective and low nonspecific binding MAO-B tracer, which can potentially be used as a surrogate marker of reactive astrogliosis.
JOURNAL OF NUCLEAR MEDICINE
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Victor L. Villemagne, Ryuichi Harada, Vincent Dore, Shozo Furumoto, Rachel Mulligan, Yukitsuka Kudo, Samantha Burnham, Natasha Krishnadas, Pierrick Bourgeat, Ying Xia, Simon Laws, Svetlana Bozinovski, Kun Huang, Milos D. Ikonomovic, Jurgen Fripp, Kazuhiko Yanai, Nobuyuki Okamura, Christopher C. Rowe
Summary: A neuroinflammatory reaction in AD brains involves reactive astrocytes that overexpress MAO-B. The PET tracer 18F-SMBT-1 showed significantly higher binding in A beta+ CN individuals and A beta+ AD patients compared to A beta-CN individuals. These findings suggest that 18F-SMBT-1 binding can be detected at the preclinical stages of A beta accumulation, supporting its use as a surrogate marker of astrogliosis in the AD continuum.
JOURNAL OF NUCLEAR MEDICINE
(2022)
Review
Neurosciences
Ryuichi Harada, Shozo Furumoto, Yukitsuka Kudo, Kazuhiko Yanai, Victor L. Villemagne, Nobuyuki Okamura
Summary: Neurodegenerative diseases are characterized by neuronal loss, gliosis, and the deposition of misfolded proteins. Imaging the glial response in vivo using PET combined with A beta and tau PET can provide insights into the disease process and aid in diagnosis and monitoring of therapeutic response.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
ShinWoo Kang, Jinho Kim, Sang-Yoon Lee, Nobuyuki Okamura, Keun-A Chang
Summary: This study used a mouse model to evaluate the pathology of Alzheimer's disease using PET imaging and found that the uptake of A beta, tau, and TSPO is age-related and correlated with age-dependent pathology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Yuto Uchida, Hirohito Kan, Keita Sakurai, Yoshihiko Horimoto, Emi Hayashi, Akihiko Iida, Nobuyuki Okamura, Kenichi Oishi, Noriyuki Matsukawa
Summary: The study aimed to examine the effect of APOE ε4 dose on BBB clearance function and its correlation with brain iron and beta-amyloid accumulation. The results showed that increased APOE ε4 dose was associated with decreased effective brain-waste clearance through the BBB.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Article
Neurosciences
Yi Li, Henry Rusinek, Tracy Butler, Lidia Glodzik, Elizabeth Pirraglia, John Babich, P. David Mozley, Sadek Nehmeh, Silky Pahlajani, Xiuyuan Wang, Emily B. Tanzi, Liangdong Zhou, Sara Strauss, Roxana O. Carare, Neil Theise, Nobuyuki Okamura, Mony J. de Leon
Summary: This study found reduced CSF clearance in Alzheimer's disease, which is associated with brain amyloid-beta deposition and cognitive decline.
FLUIDS AND BARRIERS OF THE CNS
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Keita Sakurai, Takashi Nihashi, Yasuyuki Kimura, Kaori Iwata, Hiroshi Ikenuma, Yutaka Arahata, Nobuyuki Okamura, Kazuhiko Yanai, Akio Akagi, Kengo Ito, Takashi Kato, Akinori Nakamura
Summary: This study investigated the age-related topographic change of F-18-THK5351 PET in amyloid-negative cognitively unimpaired elderly subjects. The results showed an age-dependent increase of F-18-THK5351 retention, particularly in the inferior temporal lobes, suggesting an increase in reactive astrocytes with aging.
ANNALS OF NUCLEAR MEDICINE
(2022)
Letter
Clinical Neurology
Yoshihiko Horimoto, Emi Hayashi, Nobuyuki Okamura, Aki Inagaki, Keizo Yasui, Yuto Uchida, Yoshihiro Ito, Akihiko Iida, Chikako Sato, Chise Anan, Ayuko Suzuki, Toshihisa Tajima, Hiroaki Hibino, Hidehiro Kabasawa, Noriyuki Matsukawa
MOVEMENT DISORDERS
(2022)
Article
Clinical Neurology
Ryota Kobayashi, Tadaho Nakamura, Fumito Naganuma, Ryuichi Harada, Daichi Morioka, Masafumi Kanoto, Shozo Furumoto, Yukitsuka Kudo, Takanobu Kabasawa, Koichi Otani, Mitsuru Futakuchi, Shinobu Kawakatsu, Nobuyuki Okamura
Summary: Quantification of in vivo reactive astrogliosis using [F-18]THK-5351 PET was performed to evaluate patients with neurodegenerative diseases. The study validated the imaging-pathology correlation by comparing the PET results with the autopsy brain, demonstrating that reactive astrogliosis can be identified and quantified using in vivo MAO-B imaging.
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Ryuichi Harada, Pradith Lerdsirisuk, Yuki Shimizu, Yuka Yokoyama, Yiqing Du, Kaede Kudo, Michinori Ezura, Yoichi Ishikawa, Ren Iwata, Miho Shidahara, Aiko Ishiki, Akio Kikuchi, Yuya Hatano, Tomohiko Ishihara, Osamu Onodera, Yasushi Iwasaki, Mari Yoshida, Yasuyuki Taki, Hiroyuki Arai, Yukitsuka Kudo, Kazuhiko Yanai, Shozo Furumoto, Nobuyuki Okamura
Summary: Tau PET tracer [F-18]SNFT-1 has been developed with high selectivity and affinity for tau aggregates in Alzheimer's disease brains. The tracer showed promising results for tracking age-related accumulation of tau aggregates in the human brain, with higher signal-to-background ratio compared to other tau PET tracers.
JOURNAL OF NUCLEAR MEDICINE
(2023)
Article
Neurosciences
Jae Myeong Kang, Jeong-Hyeon Shin, Woo-Ram Kim, Seongho Seo, Haeun Seo, Sang-Yoon Lee, Kee Hyung Park, Duk L. Na, Nobuyuki Okamura, Joon-Kyoung Seong, Young Noh
Summary: This study found differential effects of APOE ε4 on the relationship between tau and amyloid in patients with early-onset and late-onset Alzheimer's disease. Early-onset Alzheimer's disease ε4- patients showed more tau retention in the association cortices, while ε4+ patients had more retention in the medial temporal areas. The tau topography of late-onset Alzheimer's disease ε4+ was similar to that of early-onset Alzheimer's disease ε4+.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Fumito Naganuma, Daiki Murata, Marie Inoue, Yuri Maehori, Ryuichi Harada, Shozo Furumoto, Yukitsuka Kudo, Tadaho Nakamura, Nobuyuki Okamura
Summary: A novel NIRF probe, THK-565, was developed to noninvasively detect Aβ deposits in the brains of AD mouse models, indicating that NIRF imaging with THK-565 could be used to assess the pathological features of AD without invasive procedures.
MOLECULAR IMAGING AND BIOLOGY
(2023)
Meeting Abstract
Radiology, Nuclear Medicine & Medical Imaging
M. Tashiro, Y. Ishioka, B. T. Mesfin, A. Inamura, S. Watanuki, M. Miyake, K. Hiraoka, R. Harada, S. Furumoto, K. Yanai, N. Okamura, H. Watabe
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2022)