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Tau and PET

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https://www.readbyqxmd.com/read/28087578/distinct-binding-of-pet-ligands-pbb3-and-av-1451-to-tau-fibril-strains-in-neurodegenerative-tauopathies
#1
Maiko Ono, Naruhiko Sahara, Katsushi Kumata, Bin Ji, Ruiqing Ni, Shunsuke Koga, Dennis W Dickson, John Q Trojanowski, Virginia M-Y Lee, Mari Yoshida, Isao Hozumi, Yasumasa Yoshiyama, John C van Swieten, Agneta Nordberg, Tetsuya Suhara, Ming-Rong Zhang, Makoto Higuchi
Diverse neurodegenerative disorders are characterized by deposition of tau fibrils composed of conformers (i.e. strains) unique to each illness. The development of tau imaging agents has enabled visualization of tau lesions in tauopathy patients, but the modes of their binding to different tau strains remain elusive. Here we compared binding of tau positron emission tomography ligands, PBB3 and AV-1451, by fluorescence, autoradiography and homogenate binding assays with homologous and heterologous blockades using tauopathy brain samples...
January 12, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28077397/relationships-between-flortaucipir-pet-tau-binding-and-amyloid-burden-clinical-diagnosis-age-and-cognition
#2
Michael J Pontecorvo, Michael D Devous, Michael Navitsky, Ming Lu, Stephen Salloway, Frederick W Schaerf, Danna Jennings, Anupa K Arora, Anne McGeehan, Nathaniel C Lim, Hui Xiong, Abhinay D Joshi, Andrew Siderowf, Mark A Mintun
The advent of tau-targeted positron emission tomography tracers such as flortaucipir ((18)F-AV-1451, also known as (18)F-T807) have made it possible to investigate the sequence of development of tau and amyloid-β in relationship to age, and to the development of cognitive impairment due to Alzheimer's disease. In this study, flortaucipir tau and florbetapir amyloid positron emission tomography were obtained for 217 subjects including 16 young and 58 older cognitively normal subjects, 95 subjects with mild cognitive impairment (Mini-Mental State Examination 24-30) and 48 subjects with clinically-defined possible or probable Alzheimer's disease (Mini-Mental State Examination >10)...
January 11, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28062720/multimodal-characterization-of-older-apoe2-carriers-reveals-selective-reduction-of-amyloid-load
#3
Michel J Grothe, Sylvia Villeneuve, Martin Dyrba, David Bartrés-Faz, Miranka Wirth
OBJECTIVE: To comprehensively assess neurobiological effects of the protective APOE2 allele in the aged brain using a cross-sectional multimodal neuroimaging approach. METHODS: Multimodal neuroimaging data were obtained from a total of 572 older individuals without dementia (cognitively normal and mild cognitive impairment) enrolled in the Alzheimer's Disease Neuroimaging Initiative and included assessments of regional amyloid load with AV45-PET, glucose metabolism with fluorodeoxyglucose-PET, and gray matter volume with structural MRI...
January 6, 2017: Neurology
https://www.readbyqxmd.com/read/28013122/development-of-11-c-3-h-thk-5351-a-potential-novel-carbon-11-tau-imaging-pet-radioligand
#4
Vladimir Stepanov, Marie Svedberg, Zhisheng Jia, Raisa Krasikova, Laetitia Lemoine, Nobujuki Okamura, Shozo Furumoto, Nicholas Mitsios, Jan Mulder, Bengt Långström, Agneta Nordberg, Christer Halldin
INTRODUCTION: Due to the rise in the number of patients with dementia the imperative for finding new diagnostic and treatment options becomes ever more pressing. While significant progress has been made in PET imaging of Aβ aggregates both in vitro and in vivo, options for imaging tau protein aggregates selectively are still limited. Based on the work previously published by researchers from the Tohoku University, Japan, that resulted in the development of [(18)F]THK-5351, we have undertaken an effort to develop a carbon-11 version of the identical structure - [(11)C]THK-5351...
December 9, 2016: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/27997036/pathologic-correlations-of-f-18-av-1451-imaging-in-non-alzheimer-tauopathies
#5
Marta Marquié, Marc D Normandin, Avery C Meltzer, Michael Siao Tick Chong, Nicolas V Andrea, Alejandro Antón-Fernández, William E Klunk, Chester A Mathis, Milos D Ikonomovic, Manik Debnath, Elizabeth A Bien, Charles R Vanderburg, Isabel Costantino, Sara Makaretz, Sarah L DeVos, Derek H Oakley, Stephen N Gomperts, John H Growdon, Kimiko Domoto-Reilly, Diane Lucente, Bradford C Dickerson, Matthew P Frosch, Bradley T Hyman, Keith A Johnson, Teresa Gómez-Isla
OBJECTIVE: Recent studies have shown that PET tracer AV-1451 exhibits high binding affinity for paired helical filament (PHF)-tau pathology in Alzheimer's brains. However, the ability of this ligand to bind to tau lesions in other tauopathies remains controversial. Our goal was to examine the correlation of in vivo and postmortem AV-1451 binding patterns in three autopsy-confirmed non-Alzheimer tauopathy cases. METHODS: We quantified in vivo retention of [F-18]-AV-1451 and performed autoradiography, [H-3]-AV-1451 binding assays and quantitative tau measurements in postmortem brain samples from two Progressive Supranuclear Palsy (PSP) cases and a MAPT P301L mutation carrier...
December 20, 2016: Annals of Neurology
https://www.readbyqxmd.com/read/27956742/17q21-31-duplication-causes-prominent-tau-related-dementia-with-increased-mapt-expression
#6
K Le Guennec, O Quenez, G Nicolas, D Wallon, S Rousseau, A-C Richard, J Alexander, P Paschou, C Charbonnier, C Bellenguez, B Grenier-Boley, D Lechner, M-T Bihoreau, R Olaso, A Boland, V Meyer, J-F Deleuze, P Amouyel, H M Munter, G Bourque, M Lathrop, T Frebourg, R Redon, L Letenneur, J-F Dartigues, O Martinaud, O Kalev, S Mehrabian, L Traykov, T Ströbel, I Le Ber, P Caroppo, S Epelbaum, T Jonveaux, F Pasquier, A Rollin-Sillaire, E Génin, L Guyant-Maréchal, G G Kovacs, J-C Lambert, D Hannequin, D Campion, A Rovelet-Lecrux
To assess the role of rare copy number variations in Alzheimer's disease (AD), we conducted a case-control study using whole-exome sequencing data from 522 early-onset cases and 584 controls. The most recurrent rearrangement was a 17q21.31 microduplication, overlapping the CRHR1, MAPT, STH and KANSL1 genes that was found in four cases, including one de novo rearrangement, and was absent in controls. The increased MAPT gene dosage led to a 1.6-1.9-fold expression of the MAPT messenger RNA. Clinical signs, neuroimaging and cerebrospinal fluid biomarker profiles were consistent with an AD diagnosis in MAPT duplication carriers...
December 13, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27943341/pittsburgh-compound-b-pib-binds-amyloid-%C3%AE-protein-protofibrils
#7
Ghiam Yamin, David B Teplow
The neuropathology of Alzheimer's disease (AD) includes amyloid plaque formation by the amyloid β-protein (Aβ) and intracellular paired helical filament formation by tau protein. These neuropathogenetic features correlate with disease progression and have been revealed in brains of AD patients using positron emission tomography (PET). One of the most useful positron emission tomography imaging agents has been Pittsburgh Compound-B (PiB). However, since its introduction in 2002, substantial evidence has accumulated suggesting that Aβ oligomerization and protofibril formation, rather than fibril formation per se, may be the more important pathogenetic event in AD...
January 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27940517/tau-positron-emission-tomography-imaging
#8
Hartmuth C Kolb, José Ignacio Andrés
Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the most common cause of dementia among the elderly population. The good correlation between the density and neocortical spread of neurofibrillary tangles (NFTs) and the severity of cognitive impairment offers an opportunity to use a noninvasive imaging technique such as positron emission tomography (PET) for early diagnosis and staging of the disease. PET imaging of NFTs holds promise not only as a diagnostic tool but also because it may enable the development of disease-modifying therapeutics for AD...
December 9, 2016: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/27911319/autotaxin-is-related-to-metabolic-dysfunction-and-predicts-alzheimer-s-disease-outcomes
#9
Kelsey E McLimans, Auriel A Willette
BACKGROUND: Obesity and insulin resistance are associated with neuropathology and cognitive decline in Alzheimer's disease (AD). OBJECTIVE: Ecto-nucleotide pyrophosphatase/phosphodiesterase 2, also called autotaxin, is produced by beige adipose tissue, regulates metabolism, and is higher in AD prefrontal cortex (PFC). Autotaxin may be a novel biomarker of dysmetabolism and AD. METHODS: We studied Alzheimer's Disease Neuroimaging Initiative participants who were cognitively normal (CN; n = 86) or had mild cognitive impairment (MCI; n = 135) or AD (n = 66)...
December 1, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911289/the-brain-s-structural-connectome-mediates-the-relationship-between-regional-neuroimaging-biomarkers-in%C3%A2-alzheimer-s-disease
#10
Sneha Pandya, Amy Kuceyeski, Ashish Raj
Alzheimer's disease (AD), one of the most common causes of dementia in adults, is a progressive neurodegenerative disorder exhibiting well-defined neuropathological hallmarks. It is known that disease pathology involves misfolded amyloid-β (Aβ) and tau proteins, and exhibits a relatively stereotyped progression over decades. The relationship between AD neuropathological hallmarks (Aβ, hypometabolism, and tau proteins) and imaging biomarkers (MRI, AV-45/FDG-PET) is not fully understood. In addition, biomarker pathologies are oftentimes discordant, wherein it may show varying levels of abnormality across brain regions...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27908967/kinetic-modeling-of-the-tau-pet-tracer-18f-av-1451-in-human-healthy-volunteers-and-alzheimer-s-disease-subjects
#11
Olivier Barret, David Alagille, Sandra Sanabria, Robert A Comley, Robby M Weimer, Edilio Borroni, Mark Mintun, Nicholas Seneca, Caroline Papin, Thomas Morley, Ken Marek, John P Seibyl, Gilles D Tamagnan, Danna Jennings
: (18)F-AV-1451 is currently the most widely used of several experimental tau PET tracers. The objective of this study was to evaluate (18)F-AV-1451 binding with full kinetic analysis using a metabolite corrected arterial input function, and to compare parameters derived from kinetic analysis with standardized uptake value ratio (SUVR) calculated over different imaging time intervals. METHODS: (18)F-AV-1451 PET brain imaging was completed in 16 subjects: 4 young healthy volunteers (YHV), 4 aged healthy volunteers (AHV) and 8 Alzheimer's disease subjects (AD)...
December 1, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27903332/computerized-cognitive-tests-are-associated-with-biomarkers-of-alzheimer-s-disease-in-cognitively-normal-individuals-10-years-prior
#12
Anja Soldan, Corinne Pettigrew, Abhay Moghekar, Marilyn Albert
OBJECTIVES: Evidence suggests that Alzheimer's disease (AD) biomarkers become abnormal many years before the emergence of clinical symptoms of AD, raising the possibility that biomarker levels measured in cognitively normal individuals would be associated with cognitive performance many years later. This study examined whether performance on computerized cognitive tests is associated with levels of cerebrospinal fluid (CSF) biomarkers of amyloid, tau, and phosphorylated tau (p-tau) obtained approximately 10 years earlier, when individuals were cognitively normal and primarily middle-aged...
November 2016: Journal of the International Neuropsychological Society: JINS
https://www.readbyqxmd.com/read/27863809/efficacy-and-safety-of-tau-aggregation-inhibitor-therapy-in-patients-with-mild-or-moderate-alzheimer-s-disease-a-randomised-controlled-double-blind-parallel-arm-phase-3-trial
#13
Serge Gauthier, Howard H Feldman, Lon S Schneider, Gordon K Wilcock, Giovanni B Frisoni, Jiri H Hardlund, Hans J Moebius, Peter Bentham, Karin A Kook, Damon J Wischik, Bjoern O Schelter, Charles S Davis, Roger T Staff, Luc Bracoud, Kohkan Shamsi, John M D Storey, Charles R Harrington, Claude M Wischik
BACKGROUND: Leuco-methylthioninium bis(hydromethanesulfonate; LMTM), a stable reduced form of the methylthioninium moiety, acts as a selective inhibitor of tau protein aggregation both in vitro and in transgenic mouse models. Methylthioninium chloride has previously shown potential efficacy as monotherapy in patients with Alzheimer's disease. We aimed to determine whether LMTM was safe and effective in modifying disease progression in patients with mild to moderate Alzheimer's disease...
December 10, 2016: Lancet
https://www.readbyqxmd.com/read/27863444/av-1451-tau-and-%C3%AE-amyloid-positron-emission-tomography-imaging-in-dementia-with-lewy-bodies
#14
Kejal Kantarci, Val J Lowe, Bradley F Boeve, Matthew L Senjem, Nikki Tosakulwong, Timothy G Lesnick, Anthony J Spychalla, Jeffrey L Gunter, Julie A Fields, Jonathan Graff-Radford, Tanis J Ferman, David T Jones, Melissa E Murray, David S Knopman, Clifford R Jack, Ronald C Petersen
OBJECTIVE: Patients with probable dementia with Lewy bodies (DLB) often have Alzheimer's disease (AD)-related pathology. Our objective was to determine the pattern of positron emission tomography (PET) tau tracer AV-1451 uptake in patients with probable DLB, compared to AD, and its relationship to β-amyloid deposition on PET. METHODS: Consecutive patients with clinically probable DLB (n = 19) from the Mayo Clinic Alzheimer's Disease Research Center underwent magnetic resonance imaging, AV-1451, and Pittsburgh compound-B (PiB) PET examinations...
November 18, 2016: Annals of Neurology
https://www.readbyqxmd.com/read/27859483/a-report-of-the-automated-radiosynthesis-of-the-tau-pet-radiopharmaceutical-18-f-thk-5351
#15
Ramesh Neelamegam, Daniel L Yokell, Peter A Rice, Shozo Furumoto, Yukitsuka Kudo, Nobuyuki Okamura, Georges El Fakhri
The radiotracer, [(18) F]-THK-5351 is a highly selective and high binding affinity PET imaging agent for aggregates of hyper-phosphorylated tau protein. Our report is a simplified one-pot, two-step radiosynthesis of [(18) F]-THK-5351. This report is broadly applicable for routine clinical production and multi-center trials on account of favorable half-life of flourine-18 and the use of a commercially available radiosynthesis module, the GE TRACERlab™ FXFN . First, the O-THP protected tosyl precursor underwent nucleophilic fluorinating reaction with potassium cryptand fluoride ([(18) F] fluoride (K[(18) F]/K222 )) in DMSO at 110 °C for 10 min followed by O-THP removal by using diluted hydrochloric acid (HCl) at same temperature...
November 17, 2016: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/27856627/in-vivo-comparison-of-tau-radioligands-18f-thk-5351-and-18f-thk-5317
#16
Tobey Betthauser, Patrick J Lao, Dhanabalan Murali, Todd E Barnhart, Shozo Furumoto, Nobuyuki Okamura, Charles K Stone, Sterling C Johnson, Bradley T Christian
PURPOSE: This study compared the in vivo imaging characteristics of tau positron emission tomography (PET) ligands (18) F-THK-5351 and (18)F-THK-5317 in the context of Alzheimer's disease (AD). Additionally, reference tissue distribution volume ratio (DVR) estimation methods and standard uptake value ratio (SUVR) timing windows were evaluated to determine the optimal strategy for specific binding quantification. METHODS: Twenty-eight subjects (mean age 71±7yrs) underwent either dynamic 90-minute (18)F-THK-5317 or (18)F-THK-5351 PET scans...
November 10, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27853132/traumatic-brain-injuries
#17
Kaj Blennow, David L Brody, Patrick M Kochanek, Harvey Levin, Ann McKee, Gerard M Ribbers, Kristine Yaffe, Henrik Zetterberg
Traumatic brain injuries (TBIs) are clinically grouped by severity: mild, moderate and severe. Mild TBI (the least severe form) is synonymous with concussion and is typically caused by blunt non-penetrating head trauma. The trauma causes stretching and tearing of axons, which leads to diffuse axonal injury - the best-studied pathogenetic mechanism of this disorder. However, mild TBI is defined on clinical grounds and no well-validated imaging or fluid biomarkers to determine the presence of neuronal damage in patients with mild TBI is available...
November 17, 2016: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/27844089/-biomarkers-for-dementia-and-other-neurodegenerative-diseases-current-developments
#18
J Wiltfang, P Lewczuk, M Otto
Cerebrospinal fluid-based neurochemical dementia diagnostics (CSF-NDD) support the early and differential diagnosis of dementia, most importantly the diagnosis of early or preclinical Alzheimer's dementia (AD). Meanwhile CSF-NDD are now recommended for improved exclusion and positive diagnostics of AD by the German national neuropsychiatry S3 dementia guidelines ( www.DGPPN.de ). Meta-analyses of independent international multicenter studies have shown that a combined CSF analysis of amyloid-beta 1-42 (Aβ 1-42, decreased), total tau proteins (increased) and phospho-tau proteins (increased) offers a sensitivity and specificity of 80-90 % for the early and differential diagnosis of AD (AD versus all other)...
December 2016: Der Nervenarzt
https://www.readbyqxmd.com/read/27834776/genetic-risk-as-a-marker-of-amyloid-%C3%AE-and-tau-burden-in-cerebrospinal-fluid
#19
Nicola Voyle, Hamel Patel, Amos Folarin, Stephen Newhouse, Caroline Johnston, Pieter Jelle Visser, Richard J B Dobson, Steven J Kiddle
BACKGROUND: The search for a biomarker of Alzheimer's disease (AD) pathology (amyloid-β (Aβ) and tau) is ongoing, with the best markers currently being measurements of Aβ and tau in cerebrospinal fluid (CSF) and via positron emission tomography (PET) scanning. These methods are relatively invasive, costly, and often have high screening failure rates. Consequently, research is aiming to elucidate blood biomarkers of Aβ and tau. OBJECTIVE: This study aims to investigate a case/control polygenic risk score (PGRS) as a marker of tau and investigate blood markers of a combined Aβ and tau outcome for the first time...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27814297/cross-sectional-and-longitudinal-cognitive-correlates-of-fddnp-pet-and-csf-amyloid-%C3%AE-and-tau-in-parkinson-s-disease1
#20
Mariateresa Buongiorno, Francesca Antonelli, Yaroslau Compta, Yolanda Fernandez, Javier Pavia, Francisco Lomeña, José Ríos, Isabel Ramírez, José Ramón García, Marina Soler, Ana Cámara, Manel Fernández, Misericòrdia Basora, Fàtima Salazar, Gerard Sanchez-Etayo, Francesc Valldeoriola, Jorge Raúl Barrio, Maria Jose Marti
Tau and amyloid-β (Aβ) aggregates have been suggested to play a role in the development of dementia in Parkinson's disease (PD). Positron emission tomography (PET) with [18F]FDDNP and the determination of cerebrospinal fluid (CSF) levels of these proteins constitute a means to visualize in vivo Aβ and tau brain accumulation. Information about longitudinal changes of these CSF and PET biomarkers in PD with regard to progression to dementia is lacking. We assessed the cross-sectional and longitudinal associations of CSF and PET biomarkers of tau and Aβ with PD-related cognitive dysfunction in 6 healthy-controls (HC), 16 patients with PD without dementia (PDND), and 8 PD with dementia (PDD)...
2017: Journal of Alzheimer's Disease: JAD
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