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Tau and PET

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https://www.readbyqxmd.com/read/28210978/future-directions-in-imaging-neurodegeneration
#1
REVIEW
Joseph C Masdeu
Neuroimaging comprises a powerful set of instruments to diagnose various neurodegenerative disorders, clarifies their neurobiology, and monitors their treatment. Magnetic resonance imaging depicts volume changes, as well as abnormalities in functional and structural connectivity. Positron emission tomography (PET) allows for the quantification of regional cerebral metabolism, characteristically altered in Alzheimer's disease, amyotrophic lateral sclerosis, diffuse Lewy-body disease, and the frontotemporal dementias...
January 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28185305/cgmp-production-of-the-radiopharmaceutical-18-f-mk-6240-for-pet-imaging-of-human-neurofibrillary-tangles
#2
Thomas Lee Collier, Daniel L Yokell, Eli Livni, Peter A Rice, Sofie Celen, Kim Serdons, Ramesh Neelamegam, Guy Bormans, Dawn Harris, Abbas Walji, Eric D Hostetler, Idriss Bennacef, Neil Vasdev
Fluorine-18 labelled 6-(fluoro)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([(18) F]MK-6240) is a novel potent and selective PET radiopharmaceutical for detecting human neurofibrillary tangles, which are made up of aggregated tau protein. Herein, we report the fully automated two-step radiosynthesis of [(18) F]MK-6240 using a commercially available radiosynthesis module, GE Healthcare Tracerlab(TM) FXFN . Nucleophilic fluorination of the 5-diBoc-6-nitro precursor with potassium cryptand [(18) F]fluoride (K[(18) F]/K222 ) was carried out by conventional heating, followed by acid deprotection and semi-preparative HPLC under isocratic conditions...
February 9, 2017: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28182832/pearson-s-chi-square-test-and-rank-correlation-inferences-for-clustered-data
#3
Joanna H Shih, Michael P Fay
Pearson's chi-square test has been widely used in testing for association between two categorical responses. Spearman rank correlation and Kendall's tau are often used for measuring and testing association between two continuous or ordered categorical responses. However, the established statistical properties of these tests are only valid when each pair of responses are independent, where each sampling unit has only one pair of responses. When each sampling unit consists of a cluster of paired responses, the assumption of independent pairs is violated...
February 9, 2017: Biometrics
https://www.readbyqxmd.com/read/28138510/tau-pet-uptake-regional-variation-in-average-suvr-and-impact-of-amyloid-deposition
#4
Prashanthi Vemuri, Val J Lowe, David S Knopman, Matthew L Senjem, Bradley J Kemp, Christopher G Schwarz, Scott A Przybelski, Mary M Machulda, Ronald C Petersen, Clifford R Jack
INTRODUCTION: Tau-positron emission tomography (PET) imaging with AV1451 is sensitive to Alzheimer disease (AD)-related tau deposition in the brain. We (1) examined regional variation of average tau-PET standardized uptake value ratios (SUVRs) in a young normal population (30-49 years) and corrected for the regional variability and (2) tested if the standardized values (z-scores) scaled appropriately to capture regional Alzheimer-specific (i.e., amyloid sensitive) tau-PET changes in individuals aged 50+ years...
2017: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/28138509/association-between-a%C3%AE-and-tau-accumulations-and-their-influence-on-clinical-features-in-aging-and-alzheimer-s-disease-spectrum-brains-a-11-c-pbb3-pet-study
#5
Hitoshi Shimada, Soichiro Kitamura, Hitoshi Shinotoh, Hironobu Endo, Fumitoshi Niwa, Shigeki Hirano, Yasuyuki Kimura, Ming-Rong Zhang, Satoshi Kuwabara, Tetsuya Suhara, Makoto Higuchi
INTRODUCTION: Amyloid-β (Aβ) and tau accumulations may occur independently and concurrently as exemplified by primary age-related tauopathy and Alzheimer's disease (AD), respectively. Interactions between Aβ and tau accumulations and their influence on clinical features, however, are still unclear. METHODS: Associations among clinical symptoms, gray-matter volume, regional tau, and Aβ deposition assessed by positron emission tomography with [(11)C]pyridinyl-butadienyl-benzothiazole 3 (PBB3) and [(11)C]Pittsburgh compound-B (PiB), were evaluated in 17 AD, 9 mild cognitive impairment due to AD, and 28 PiB(-)-cognitive healthy controls (HCs)...
2017: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/28130473/frontotemporal-dementia-with-the-v337m-mapt-mutation-tau-pet-and-pathology-correlations
#6
Salvatore Spina, Daniel R Schonhaut, Bradley F Boeve, William W Seeley, Rik Ossenkoppele, James P O'Neil, Andreas Lazaris, Howard J Rosen, Adam L Boxer, David C Perry, Bruce L Miller, Dennis W Dickson, Joseph E Parisi, William J Jagust, Melissa E Murray, Gil D Rabinovici
OBJECTIVE: To assess the efficacy of [(18)F]AV1451 PET in visualizing tau pathology in vivo in a patient with frontotemporal dementia (FTD) associated with the V337M microtubule-associated protein tau (MAPT) mutation. METHODS: MAPT mutations are associated with the deposition of hyperphosphorylated tau protein in neurons and glia. The PET tracer [(18)F]AV1451 binds with high affinity to paired helical filaments tau that comprises neurofibrillary tangles in Alzheimer disease (AD), while postmortem studies suggest lower or absent binding to the tau filaments of the majority of non-AD tauopathies...
January 27, 2017: Neurology
https://www.readbyqxmd.com/read/28108013/detection-of-extra-regional-tumour-recurrence-with-18-f-fdg-pet-ct-in-patients-with-recurrent-gynaecological-malignancies-being-considered-for-radical-salvage-surgery
#7
H Brar, T May, N Tau, D Langer, P MacCrostie, K Han, U Metser
AIM: To compare the detection rate of extra-regional metastases in patients with recurrent gynaecological malignancies being considered for radical salvage surgery with combined 2-[(18)F]-fluoro-2-deoxy-d-glucose ((18)F-FDG) positron-emission tomography (PET)/computed tomography (CT) compared to conventional imaging. MATERIALS AND METHODS: A retrospective review was performed of all patients in a provincial database with recurrent gynaecological malignancies being considered for pelvic exenteration that underwent restaging with CT/PET between March 2011 and October 2014...
January 17, 2017: Clinical Radiology
https://www.readbyqxmd.com/read/28106992/discovery-of-n-pyridin-4-yl-1-5-naphthyridin-2-amines-as-potential-tau-pathology-pet-tracers-for-alzheimer-s-disease
#8
Frederik J R Rombouts, José-Ignacio Andrés, Manuela Ariza, José Manuel Alonso, Nigel Austin, Astrid Bottelbergs, Lu Chen, Vladimir Chupakhin, Erna Cleiren, Katleen Fierens, Alberto Fontana, Xavier Langlois, Joseph E Leenaerts, Jonas Mariën, Carolina Martínez Lamenca, Rhys Salter, Mark E Schmidt, Paula Te Riele, Cindy Wintmolders, Andrés A Trabanco, Wei Zhang, Gregor Macdonald, Dieder Moechars
A mini-HTS on 4000 compounds selected using 2D fragment-based similarity and 3D pharmacophoric and shape similarity to known selective tau aggregate binders identified N-(6-methylpyridin-2-yl)quinolin-2-amine 10 as a novel potent binder to human AD aggregated tau with modest selectivity versus aggregated β-amyloid (Aβ). Initial medicinal chemistry efforts identified key elements for potency and selectivity, as well as suitable positions for radiofluorination, leading to a first generation of fluoroalkyl-substituted quinoline tau binding ligands with suboptimal physicochemical properties...
February 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28097206/-18-f-av-1451-pet-in-behavioral-variant-frontotemporal-dementia-due-to-mapt-mutation
#9
W Richard Bevan Jones, Thomas E Cope, Luca Passamonti, Tim D Fryer, Young T Hong, Franklin Aigbirhio, Jillian J Kril, Shelley L Forrest, Kieren Allinson, Jonathan P Coles, P Simon Jones, Maria G Spillantini, John R Hodges, John T O'Brien, James B Rowe
The validation of tau radioligands could improve the diagnosis of frontotemporal lobar degeneration and the assessment of disease-modifying therapies. Here, we demonstrate that binding of the tau radioligand [(18)F]AV-1451 was significantly abnormal in both magnitude and distribution in a patient with familial frontotemporal dementia due to a MAPT 10 + 16C>T gene mutation, recapitulating the pattern of neuropathology seen in her father. Given the genetic diagnosis and the non-Alzheimer's pathology, these findings suggest that [(18)F]AV-1451 might be a useful biomarker in primary tauopathies...
December 2016: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28097205/impact-of-tau-and-amyloid-burden-on-glucose-metabolism-in-alzheimer-s-disease
#10
Gérard N Bischof, Frank Jessen, Klaus Fliessbach, Julian Dronse, Jochen Hammes, Bernd Neumaier, Oezguer Onur, Gereon R Fink, Juraj Kukolja, Alexander Drzezga, Thilo van Eimeren
In a multimodal PET imaging approach, we determined the differential contribution of neurofibrillary tangles (measured with [(18)F]AV-1451) and beta-amyloid burden (measured with [(11)C]PiB) on degree of neurodegeneration (i.e., glucose metabolism measured with [(18)F]FDG-PET) in patients with Alzheimer's disease. Across brain regions, we observed an interactive effect of beta-amyloid burden and tau deposition on glucose metabolism which was most pronounced in the parietal lobe. Elevated beta-amyloid burden was associated with a stronger influence of tau accumulation on glucose metabolism...
December 2016: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28087578/distinct-binding-of-pet-ligands-pbb3-and-av-1451-to-tau-fibril-strains-in-neurodegenerative-tauopathies
#11
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
#12
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
#13
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
#14
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/pathological-correlations-of-f-18-av-1451-imaging-in-non-alzheimer-tauopathies
#15
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 positron emission tomography (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...
January 2017: Annals of Neurology
https://www.readbyqxmd.com/read/27956742/17q21-31-duplication-causes-prominent-tau-related-dementia-with-increased-mapt-expression
#16
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
#17
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
#18
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
#19
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
#20
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
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