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Tau and PET

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https://www.readbyqxmd.com/read/28900724/hypothalamic-dysfunction-is-related-to-sleep-impairment-and-csf-biomarkers-in-alzheimer-s-disease
#1
Claudio Liguori, Agostino Chiaravalloti, Marzia Nuccetelli, Francesca Izzi, Giuseppe Sancesario, Andrea Cimini, Sergio Bernardini, Orazio Schillaci, Nicola Biagio Mercuri, Placidi Fabio
Hypothalamus is a key brain region regulating several essential homeostatic functions, including the sleep-wake cycle. Alzheimer's disease (AD) pathology affects nuclei controlling sleep-wake rhythm sited in this brain area. Since only post-mortem studies documented the relationship between hypothalamic atrophy and sleep-wake cycle impairment, we investigated in AD patients the possible hypothalamic in vivo alteration using 2-deoxy-2-(18F) fluoro-D-glucose ([18F]FDG) positron emission tomography ([18F]FDG PET), and its correlations with sleep impairment and cerebrospinal-fluid (CSF) AD biomarkers (tau proteins and β-amyloid42)...
September 12, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28890300/tau-positron-emission-tomography-using-18-f-thk5351-and-cerebral-glucose-hypometabolism-in-alzheimer-s-disease
#2
Jae Myeong Kang, Sang-Yoon Lee, Seongho Seo, Hye Jin Jeong, Sung-Ho Woo, Hyon Lee, Yeong-Bae Lee, Byeong Kil Yeon, Dong Hoon Shin, Kee Hyung Park, Hyejin Kang, Nobuyuki Okamura, Shozo Furumoto, Kazuhiko Yanai, Victor L Villemagne, Joon-Kyung Seong, Duk L Na, Tatsuo Ido, Jaelim Cho, Kyoung-Min Lee, Young Noh
This study aims to evaluate the clinical validity of [(18)F]THK5351 positron emission tomography (PET) for the assessment of disease progression and symptoms in Alzheimer's disease (AD). Fifty-one patients with AD dementia, 30 patients with amnestic mild cognitive impairment (aMCI), and 43 controls with normal cognition (NC) were included. All subjects underwent [(18)F]THK5351 PET, 3.0-T magnetic resonance imaging, and detailed neuropsychological tests. Regions of interest and voxel-based statistical analyses were performed...
August 12, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28887599/uptake-of-av-1451-in-meningiomas
#3
Tyler J Bruinsma, Derek R Johnson, Ping Fang, Matthew Senjem, Keith A Josephs, Jennifer L Whitwell, Bradley F Boeve, Mukesh K Pandey, Kejal Kantarci, David T Jones, Prashanthi Vemuri, Melissa Murray, Jonathan Graff-Radford, Christopher G Schwarz, David S Knopman, Ronald C Petersen, Clifford R Jack, Val J Lowe
AIM: AV-1451 is an imaging agent labeled with the positron-emitting radiolabel Fluorine-18. 18F-AV-1451 binds paired helical filament tau (PHF-tau), a pathology related to Alzheimer's disease. In our study of AV-1451 uptake in the brains of cognitively normal subjects, we noted a case of a meningioma with visually significant uptake of AV-1451. OBJECTIVE: We initiated the present retrospective study to further examine cases of meningioma that underwent AV-1451 imaging...
September 8, 2017: Annals of Nuclear Medicine
https://www.readbyqxmd.com/read/28884232/-18-f-av-1451-binding-to-neuromelanin-in-the-substantia-nigra-in-pd-and-psp
#4
Sarah Coakeley, Sang Soo Cho, Yuko Koshimori, Pablo Rusjan, Christine Ghadery, Jinhee Kim, Anthony E Lang, Sylvain Houle, Antonio P Strafella
This study investigated binding of [(18)F]AV-1451 to neuromelanin in the substantia nigra of patients with Parkinson's disease (PD) and progressive supranuclear palsy (PSP). [(18)F]AV-1451 is a positron emission tomography radiotracer designed to bind pathological tau. A post-mortem study using [(18)F]AV-1451 discovered off-target binding properties to neuromelanin in the substantia nigra. A subsequent clinical study reported a 30% decrease in [(18)F]AV-1451 binding in the midbrain of PD patients. A total of 12 patients and 10 healthy age-matched controls were recruited...
September 7, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28869470/the-cerebrospinal-fluid-a%C3%AE-1-42-a%C3%AE-1-40-ratio-improves-concordance-with-amyloid-pet-for-diagnosing-alzheimer-s-disease-in-a-clinical-setting
#5
Ellis Niemantsverdriet, Julie Ottoy, Charisse Somers, Ellen De Roeck, Hanne Struyfs, Femke Soetewey, Jeroen Verhaeghe, Tobi Van den Bossche, Sara Van Mossevelde, Johan Goeman, Peter Paul De Deyn, Peter Mariën, Jan Versijpt, Kristel Sleegers, Christine Van Broeckhoven, Leonie Wyffels, Adrien Albert, Sarah Ceyssens, Sigrid Stroobants, Steven Staelens, Maria Bjerke, Sebastiaan Engelborghs
BACKGROUND: Evidence suggests that the concordance between amyloid-PET and cerebrospinal fluid (CSF) amyloid-β (Aβ) increases when the CSF Aβ1-42/Aβ1-40 ratio is used as compared to CSF Aβ1-42 levels alone. OBJECTIVE: In order to test this hypothesis, we set up a prospective longitudinal study comparing the concordance between different amyloid biomarkers for Alzheimer's disease (AD) in a clinical setting. METHODS: Seventy-eight subjects (AD dementia (n = 17), mild cognitive impairment (MCI, n = 48), and cognitively healthy controls (n = 13)) underwent a [18F]Florbetapir ([18F]AV45) PET scan, [18F]FDG PET scan, MRI scan, and an extensive neuropsychological examination...
September 1, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28864633/correlations-of-18-f-thk5351-pet-with-post-mortem-burden-of-tau-and-astrogliosis-in-alzheimer-s-disease
#6
Ryuichi Harada, Aiko Ishiki, Hideaki Kai, Naomi Sato, Katsutoshi Furukawa, Shozo Furumoto, Tetsuro Tago, Naoki Tomita, Shoichi Watanuki, Kotaro Hiraoka, Yoichi Ishikawa, Yoshihito Funaki, Tadaho Nakamura, Takeo Yoshikawa, Ren Iwata, Manabu Tashiro, Hironobu Sasano, Tetsuyuki Kitamoto, Kazuhiko Yanai, Hiroyuki Arai, Yukitsuka Kudo, Nobuyuki Okamura
Clinical PET studies using (18)F-THK5351 have demonstrated significant tracer retention in sites susceptible to tau burden in Alzheimer's disease (AD). However, the in vivo PET signal to reflect tau aggregates remains controversial. Methods: We examined the spatial pattern of tracer binding, amyloid-β, tau and gliosis in an autopsy-confirmed AD case who underwent (18)F-THK5351 and (11)C-PiB PET before death. Results: Regional in vivo (18)F-THK5351 retention was significantly correlated with the density of tau aggregates in the neocortex and monoamine oxidase-B (MAO-B) in the whole brain, but not correlated with that of insoluble amyloid-β...
September 1, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28857559/rational-design-of-in-vivo-tau-tangle-selective-near-infrared-fluorophores-expanding-the-bodipy-universe
#7
Peter Verwilst, Hye-Ri Kim, Jinho Seo, Nak-Won Sohn, Seung-Yun Cha, Yeongmin Kim, Sungho Maeng, Jung-Won Shin, Jong Hwan Kwak, Chulhun Kang, Jong Seung Kim
The elucidation of the cause of Alzheimer's disease remains one of the greatest questions in neurodegenerative research. The lack of highly reliable low-cost sensors to study the structural changes in key proteins during the progression of the disease is a contributing factor to this lack of insight. In the current work, we describe the rational design and synthesis of two fluorescent BODIPY-based probes, named Tau 1 and Tau 2. The probes were evaluated on the molecular surface formed by a fibril of the PHF6 ((306)VQIVYK(311)) tau fragment using molecular docking studies to provide a potential molecular model to rationalize the selectivity of the new probes as compared to a homologous Aβ-selective probe...
September 15, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28856235/regional-tau-deposition-and-subregion-atrophy-of-medial-temporal-structures-in-early-alzheimer-s-disease-a-combined-positron-emission-tomography-magnetic-resonance-imaging-study
#8
Daichi Sone, Etsuko Imabayashi, Norihide Maikusa, Nobuyuki Okamura, Shozo Furumoto, Yukitsuka Kudo, Masayo Ogawa, Harumasa Takano, Yuma Yokoi, Masuhiro Sakata, Tadashi Tsukamoto, Koichi Kato, Hiroshi Matsuda
INTRODUCTION: Molecular imaging and selective hippocampal subfield atrophy are a focus of recent Alzheimer's disease (AD) research. Here, we investigated correlations between molecular imaging and hippocampal subfields in early AD. METHODS: We investigated 18 patients with early AD and 18 healthy control subjects using (11)C-Pittsburgh compound-B (PIB) positron emission tomography (PET) and (18)F-THK5351 PET and automatic segmentation of hippocampal subfields with high-resolution T2-weighted magnetic resonance imaging...
2017: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/28826526/small-molecule-pet-tracers-for-imaging-proteinopathies
#9
REVIEW
Chester A Mathis, Brian J Lopresti, Milos D Ikonomovic, William E Klunk
In this chapter, we provide a review of the challenges and advances in developing successful PET imaging agents for 3 major types of aggregated amyloid proteins: amyloid-beta (Aβ), tau, and alpha-synuclein (α-syn). These 3 amyloids are involved in the pathogenesis of a variety of neurodegenerative diseases, referred to as proteinopathies or proteopathies, that include Alzheimer disease, Lewy body dementias, multiple system atrophy, and frontotemporal dementias, among others. In the Introduction section, we briefly discuss the history of amyloid in neurodegenerative diseases and describe why progress in developing effective imaging agents has been hampered by the failure of crystallography to provide definitive ligand-protein interactions for rational radioligand design efforts...
September 2017: Seminars in Nuclear Medicine
https://www.readbyqxmd.com/read/28814462/-18-f-av-1451-binds-to-motor-related-subcortical-gray-and-white-matter-in-corticobasal-syndrome
#10
Hanna Cho, Min Seok Baek, Jae Yong Choi, Seung Ha Lee, Joong Seok Kim, Young Hoon Ryu, Myung Sik Lee, Chul Hyoung Lyoo
OBJECTIVE: To investigate tau distribution in patients with corticobasal syndrome (CBS) using (18)F-AV-1451 PET. METHODS: Six consecutively recruited patients with CBS and 20 age-matched healthy controls underwent 2 PET scans with (18)F-AV-1451 (for tau) and (18)F-florbetaben (for β-amyloid). We compared standardized uptake value ratio maps of the (18)F-AV-1451 PET images between the patients with CBS and controls. RESULTS: Compared to controls, patients with CBS exhibited asymmetrically increased (18)F-AV-1451 binding in the putamen, globus pallidus, and thalamus contralateral to the clinically more affected side and in the ipsilateral globus pallidus and dentate nucleus...
September 12, 2017: Neurology
https://www.readbyqxmd.com/read/28808912/molecular-imaging-and-updated-diagnostic-criteria-in-lewy-body-dementias
#11
REVIEW
Nicolaas I Bohnen, Martijn L T M Müller, Kirk A Frey
PURPOSE OF REVIEW: The aims of the study were to review recent advances in molecular imaging in the Lewy body dementias (LBD) and determine if these may support the clinical but contested temporal profile distinction between Parkinson disease (PD) with dementia (PDD) versus dementia with Lewy bodies (DLB). RECENT FINDINGS: There do not appear to be major regional cerebral metabolic or neurotransmitter distinctions between PDD and DLB. However, recent studies highlight the relative discriminating roles of Alzheimer proteinopathies...
August 14, 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28804110/current-and-future-prospects-of-nuclear-medicine-in-dementia
#12
Kengo Ito, Yoshiki Inui, Tsuyoshi Kizawa, Yasuyuki Kimura, Takashi Kato
In clinical diagnostic imaging of Alzheimer's disease (AD), MRI and nuclear medicine studies such as cerebral blood flow SPECT are positioned as biomarkers expressing pathological conditions. With understanding its usefulness and limitations, it is important to conduct appropriate application and to utilize the correct evaluation of the result in clinical practice. Although FDG-PET and amyloid PET are still not covered for dementia by health insurance, they are extremely useful for differential diagnosis as well as early diagnosis of AD...
August 11, 2017: Rinshō Shinkeigaku, Clinical Neurology
https://www.readbyqxmd.com/read/28803444/atypical-parkinsonian-syndromes-a-general-neurologist-s-perspective
#13
REVIEW
Angela B Deutschländer, Owen A Ross, Dennis W Dickson, Zbigniew K Wszolek
The differential diagnosis of atypical parkinsonian syndromes is challenging. These severe and often rapidly progressive neurodegenerative disorders are clinically heterogeneous and show significant phenotypic overlap. Here we review clinical, imaging, neuropathologic and genetic features of multiple system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and frontotemporal lobar degeneration (FTLD). The terms CBD and FTLD refer to pathologically confirmed cases of corticobasal syndrome (CBS) and frontotemporal dementia (FTD)...
August 12, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/28800330/pet-tau-and-amyloid-%C3%AE-burden-in-mild-alzheimer-s-disease-divergent-relationship-with-age-cognition-and-cerebrospinal-fluid-biomarkers
#14
Ivan Koychev, Roger N Gunn, Azadeh Firouzian, Jennifer Lawson, Giovanna Zamboni, Basil Ridha, Barbara J Sahakian, James B Rowe, Alan Thomas, Lynn Rochester, Dominic Ffytche, Robert Howard, Henrik Zetterberg, Clare MacKay, Simon Lovestone
BACKGROUND: Combining PET amyloid-β (Aβ) and tau imaging may be critical for tracking disease progression in Alzheimer's disease (AD). OBJECTIVE: We sought to characterize the relationship between Aβ and tau ligands as well as with other measures of pathology. METHODS: We conducted a multi-center observational study in early AD (MMSE >20) participants aged 50 to 85 y. The schedule included cognitive assessments (ADAS-Cog) and CSF measurement of Aβ and tau at baseline and 6 months; PET-CT imaging with Aβ ([18F]AV45) and tau ([18F]AV1451) ligands at baseline...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28790016/tau-imaging-in-neurodegeneration
#15
REVIEW
Gérard N Bischof, Heike Endepols, Thilo van Eimeren, Alexander Drzezga
Pathological cerebral aggregations of proteins are suggested to play a crucial role in the development of neurodegenerative disorders. For example, aggregation of the protein ß-amyloid in form of extracellular amyloid-plaques as well as intraneuronal depositions of the protein tau in form of neurofibrillary tangles represent hallmarks of Alzheimer's disease (AD). Recently, novel tracers for in vivo molecular imaging of tau-aggregates in the brain have been introduced, complementing existing tracers for imaging amyloid-plaques...
August 5, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28758146/effects-of-traumatic-brain-injury-and-posttraumatic-stress-disorder-on-development-of-alzheimer-s-disease-in-vietnam-veterans-using-the-alzheimer-s-disease-neuroimaging-initiative-preliminary-report
#16
Michael W Weiner, Danielle Harvey, Jacqueline Hayes, Susan M Landau, Paul S Aisen, Ronald C Petersen, Duygu Tosun, Dallas P Veitch, Clifford R Jack, Charles Decarli, Andrew J Saykin, Jordan Grafman, Thomas C Neylanthe
INTRODUCTION: Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) have previously been reported to be associated with increased risk of Alzheimer's disease (AD). We are using biomarkers to study Vietnam Veterans with/without mild cognitive impairment with a history of at least one TBI and/or ongoing PTSD to determine whether these contribute to the development of AD. METHODS: Potential subjects identified by Veterans Administration records underwent an initial telephone screen...
June 2017: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/28756238/av-1451-pet-imaging-of-tau-pathology-in-preclinical-alzheimer-disease-defining-a-summary-measure
#17
Shruti Mishra, Brian A Gordon, Yi Su, Jon Christensen, Karl Friedrichsen, Kelley Jackson, Russ Hornbeck, David A Balota, Nigel J Cairns, John C Morris, Beau M Ances, Tammie L S Benzinger
Utilizing [18F]-AV-1451 tau positron emission tomography (PET) as an Alzheimer disease (AD) biomarker will require identification of brain regions that are most important in detecting elevated tau pathology in preclinical AD. Here, we utilized an unsupervised learning, data-driven approach to identify brain regions whose tau PET is most informative in discriminating low and high levels of [18F]-AV-1451 binding. 84 cognitively normal participants who had undergone AV-1451 PET imaging were used in a sparse k-means clustering with resampling analysis to identify the regions most informative in dividing a cognitively normal population into high tau and low tau groups...
July 26, 2017: NeuroImage
https://www.readbyqxmd.com/read/28750496/tau-imaging-with-pet-an-overview-of-challenges-current-progress-and-future-applications
#18
Joanne S Robertson, Christopher C Rowe, Victor L Villemagne
Folded and misfolded tau is common to many neurodegenerative conditions, collectively termed 'tauopathies'. In recent years, many efforts have contributed toward development of tau imaging agents to allow measurement of tau deposits in vivo using Positron Emission Tomography (PET). The particularities of tau present some unique challenges for the development of tau imaging tracers. Most notably, these pertain to the predominantly intracellular nature of tau aggregations, the existence of six isoforms, multiple post-translational modification, and that tau is usually surrounded by larger concentrations of A plaques...
July 27, 2017: Quarterly Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28747523/-18-f-flortaucipir-pet-mri-correlations-in-non-amnestic-and-amnestic-variants-of-alzheimer-disease
#19
Ilya M Nasrallah, Yin Jie Chen, Meng-Kang Hsieh, Jeffrey S Philips, Kylie Ternes, Grace Stockbower, Yvette Sheline, Corey T McMillan, Murray Grossman, David A Wolk
Non-amnestic Alzheimer disease (AD) variants, including posterior cortical atrophy (PCA) and logopenic variant of primary progressive aphasia (lvPPA), differ in distributions of tau aggregates and neurodegeneration compared to amnestic AD. We evaluated whether (18)F-flortaucipir (also called (18)F-AV-1451) Positron Emission Tomography (PET), targeting tau aggregates, detects these differences and compared this to magnetic resonance imaging (MRI) measures of gray matter (GM) atrophy. Methods: 5 PCA, 4 lvPPA, 6 age-matched AD, and 6 control subjects underwent (18)F-flortaucipir PET and MRI...
July 26, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28743782/-18-f-av-1451-and-csf-t-tau-and-p-tau-as-biomarkers-in-alzheimer-s-disease
#20
Niklas Mattsson, Michael Schöll, Olof Strandberg, Ruben Smith, Sebastian Palmqvist, Philip S Insel, Douglas Hägerström, Tomas Ohlsson, Henrik Zetterberg, Jonas Jögi, Kaj Blennow, Oskar Hansson
To elucidate the relationship between cerebrospinal fluid (CSF) total-tau (T-tau) and phosphorylated tau (P-tau) with the tau PET ligand (18)F-AV-1451 in Alzheimer's disease (AD), we examined 30 cognitively healthy elderly (15 with preclinical AD), 14 prodromal AD, and 39 AD dementia patients. CSF T-tau and P-tau were highly correlated (R = 0.92, P < 0.001), but they were only moderately associated with retention of (18)F-AV-1451, and mainly in demented AD patients. (18)F-AV-1451, but not CSF T-tau or P-tau, was strongly associated with atrophy and cognitive impairment...
September 2017: EMBO Molecular Medicine
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