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Tau and PET

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https://www.readbyqxmd.com/read/27911319/autotaxin-is-related-to-metabolic-dysfunction-and-predicts-alzheimer-s-disease-outcomes
#1
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
#2
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...
November 28, 2016: 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
#3
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
#4
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
#5
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...
November 15, 2016: Lancet
https://www.readbyqxmd.com/read/27863444/av-1451-tau-and-%C3%AE-amyloid-pet-imaging-in-dementia-with-lewy-bodies
#6
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 often have Alzheimer's disease-related pathology. Our objective was to determine the pattern of positron emission tomography tau tracer AV-1451 uptake in patients with probable dementia with Lewy bodies, compared to Alzheimer's disease, and its relationship to β-amyloid deposition on positron emission tomography. METHODS: Consecutive patients with clinically probable dementia with Lewy bodies (n=19) from the Mayo Clinic Alzheimer's Disease Research Center underwent MRI, AV-1451 and Pittsburgh compound-B positron emission tomography 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
#7
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
#8
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
#9
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
#10
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
#11
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...
November 6, 2016: 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
#12
Mariateresa Buongiorno, Francesca Antonelli, Yaroslau Compta, Yolanda Fernandez, Javier Pavia, Francisco Lomeña, José Ríos, Isabel Ramírez, José Ramón Garía, Marina Soler, Ana Cámara, Manel Fernández, Misericòrdia Basora, Fáima 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)...
November 3, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27813160/subcortical-18-f-av-1451-binding-patterns-in-progressive-supranuclear-palsy
#13
Hanna Cho, Jae Yong Choi, Mi Song Hwang, Seung Ha Lee, Young Hoon Ryu, Myung Sik Lee, Chul Hyoung Lyoo
BACKGROUND: Accumulation of cortical and subcortical tau pathology is the primary pathological substrate for progressive supranuclear palsy (PSP). (18) F-AV-1451, a radiotracer that binds to the pathological tau protein, may be helpful for in vivo visualization and quantitation of tau pathology in PSP. OBJECTIVES: The objectives of this study were to investigate cortical and subcortical (18) F-AV-1451 binding patterns in patients with PSP. METHODS: We recruited 14 PSP patients and compared their cortical and subcortical binding patterns in (18) F-AV-1451 positron emission tomography (PET) studies with those of 15 Parkinson's disease (PD) patients and 15 healthy controls...
November 3, 2016: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/27806705/neuroimaging-in-vascular-cognitive-impairment-a-state-of-the-art-review
#14
REVIEW
Wolf-Dieter Heiss, Gary A Rosenberg, Alexander Thiel, Rok Berlot, Jacques de Reuck
Imaging is critical in the diagnosis and treatment of dementia, particularly in vascular cognitive impairment, due to the visualization of ischemic and hemorrhagic injury of gray and white matter. Magnetic resonance imaging (MRI) and positron emission tomography (PET) provide structural and functional information. Clinical MRI is both generally available and versatile - T2-weighted images show infarcts, FLAIR shows white matter changes and lacunar infarcts, and susceptibility-weighted images reveal microbleeds...
November 3, 2016: BMC Medicine
https://www.readbyqxmd.com/read/27805971/recent-advances-in-cerebrospinal-fluid-biomarkers-for-the-detection-of-preclinical-alzheimer-s-disease
#15
Luka Kulic, Paul G Unschuld
PURPOSE OF REVIEW: The concept of preclinical Alzheimer's disease has emerged to describe the long 'silent' phase of the disease when significant pathophysiological changes occur in the brain but clinical symptoms are not yet manifest. In this review, a summary of the recent advances in cerebrospinal fluid (CSF) biomarker-based diagnostics of preclinical Alzheimer's disease will be presented. RECENT FINDINGS: The association between core CSF biomarkers of Alzheimer's disease and between CSF and neuroimaging markers has been a major focus of various recently published studies in cognitively healthy individuals...
December 2016: Current Opinion in Neurology
https://www.readbyqxmd.com/read/27802224/in-vivo-patterns-of-tau-pathology-amyloid-%C3%AE-burden-and-neuronal-dysfunction-in-clinical-variants-of-alzheimer-s-disease
#16
Julian Dronse, Klaus Fliessbach, Gérard N Bischof, Boris von Reutern, Jennifer Faber, Jochen Hammes, Georg Kuhnert, Bernd Neumaier, Oezguer A Onur, Juraj Kukolja, Thilo van Eimeren, Frank Jessen, Gereon R Fink, Thomas Klockgether, Alexander Drzezga
The clinical heterogeneity of Alzheimer's disease is not reflected in the rather diffuse cortical deposition of amyloid-β. We assessed the relationship between clinical symptoms, in vivo tau pathology, amyloid distribution, and hypometabolism in variants of Alzheimer's disease using novel multimodal PET imaging techniques. Tau pathology was primarily observed in brain regions related to clinical symptoms and overlapped with areas of hypometabolism. In contrast, amyloid-β deposition was diffusely distributed over the entire cortex...
October 11, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27797445/tau-imaging-with-18-f-thk-5351-in-progressive-supranuclear-palsy
#17
A Ishiki, R Harada, N Okamura, N Tomita, C C Rowe, V L Villemagne, K Yanai, Y Kudo, H Arai, S Furumoto, M Tashiro, K Furukawa
BACKGROUND AND PURPOSE: Visualization of pathogenic protein aggregates is crucial to elucidate pathomechanisms and to make an accurate diagnosis in many neurodegenerative conditions. Aggregates of the microtubule-binding protein, tau, are one of the most important pathogenic molecules in neurodegenerative disorders. Progressive supranuclear palsy (PSP) is characterized by the deposition of tau proteins in some specific area such as the basal ganglia and brainstem. We tried to detect tau lesions in the brains of living patients with PSP with a novel positron emission tomography (PET) tracer, [(18) F]THK-5351, which we have recently developed...
October 31, 2016: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/27794115/in-vivo-visualization-of-tau-deposits-in-corticobasal-syndrome-by-18f-thk5351-pet
#18
Akio Kikuchi, Nobuyuki Okamura, Takafumi Hasegawa, Ryuichi Harada, Shoichi Watanuki, Yoshihito Funaki, Kotaro Hiraoka, Toru Baba, Naoto Sugeno, Ryuji Oshima, Shun Yoshida, Junpei Kobayashi, Michinori Ezura, Michiko Kobayashi, Ohito Tano, Shunji Mugikura, Ren Iwata, Aiko Ishiki, Katsutoshi Furukawa, Hiroyuki Arai, Shozo Furumoto, Manabu Tashiro, Kazuhiko Yanai, Yukitsuka Kudo, Atsushi Takeda, Masashi Aoki
OBJECTIVE: To determine whether (18)F-THK5351 PET can be used to visualize tau deposits in brain lesions in live patients with corticobasal syndrome (CBS). METHODS: We evaluated the in vitro binding of (3)H-THK5351 in postmortem brain tissues from a patient with corticobasal degeneration (CBD). In clinical PET studies, (18)F-THK5351 retention in 5 patients with CBS was compared to that in 8 age-matched normal controls and 8 patients with Alzheimer disease (AD). RESULTS: (3)H-THK5351 was able to bind to tau deposits in the postmortem brain with CBD...
November 29, 2016: Neurology
https://www.readbyqxmd.com/read/27765859/modeling-strategies-for-quantification-of-in-vivo-18f-av1451-binding-in-patients-with-tau-pathology
#19
Andreas Hahn, Martin Schain, Maria Erlandsson, Petter Sjölin, Gregory M James, Olof T Strandberg, Douglas Hägerström, Rupert Lanzenberger, Jonas Jögi, Tomas G Olsson, Ruben Smith, Oskar Hansson
: Aggregation of hyperphosphorylated tau is a major hallmark of many neurodegenerative diseases, including Alzheimer's disease. In vivo imaging with positron emission tomography (PET) may offer important insights in pathophysiological mechanisms, diagnosis and disease progression. We describe different strategies for quantification of (18)F-AV1451 (T807) tau binding, including models with blood sampling and non-invasive alternatives. METHODS: 15 subjects (4 controls, 6 Alzheimer's disease (AD), 3 progressive supranuclear palsy (PSP), 2 cortico basal syndrome (CBS)) underwent 180 min PET with (18)F-AV1451 and arterial blood sampling...
October 20, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27764160/csf-biomarkers-and-its-associations-with-18f-av133-cerebral-vmat2-binding-in-parkinson-s-disease-a-preliminary-report
#20
Rui Gao, Guangjian Zhang, Xueqi Chen, Aimin Yang, Gwenn Smith, Dean F Wong, Yun Zhou
OBJECTIVE: Cerebrospinal fluid (CSF) biomarkers, such as α-synuclein (α-syn), amyloid beta peptide 1-42 (Aβ1-42), phosphorylated tau (181P) (p-tau), and total tau (t-tau), have long been associated with the development of Parkinson disease (PD) and other neurodegenerative diseases. In this investigation, we reported the assessment of CSF biomarkers and their correlations with vesicular monoamine transporter 2 (VMAT2) bindings measured with 18F-9-fluoropropyl-(+)-dihydrotetrabenazine (18F-AV133) that is being developed as a biomarker for PD...
2016: PloS One
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