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Tau and PET

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
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
Sven Haller, Greg Zaharchuk, David L Thomas, Karl-Olof Lovblad, Frederik Barkhof, Xavier Golay
Arterial spin labeling (ASL) is a magnetic resonance (MR) imaging technique used to assess cerebral blood flow noninvasively by magnetically labeling inflowing blood. In this article, the main labeling techniques, notably pulsed and pseudocontinuous ASL, as well as emerging clinical applications will be reviewed. In dementia, the pattern of hypoperfusion on ASL images closely matches the established patterns of hypometabolism on fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) images due to the close coupling of perfusion and metabolism in the brain...
November 2016: Radiology
Shubir Dutt, Richard J Binney, Hilary W Heuer, Phi Luong, Suneth Attygalle, Priyanka Bhatt, Gabe A Marx, Jonathan Elofson, Maria C Tartaglia, Irene Litvan, Scott M McGinnis, Bradford C Dickerson, John Kornak, Dana Waltzman, Lisa Voltarelli, Norbert Schuff, Gil D Rabinovici, Joel H Kramer, Clifford R Jack, Bruce L Miller, Howard J Rosen, Adam L Boxer
OBJECTIVE: To examine the utility and reliability of volumetric MRI in measuring disease progression in the 4 repeat tauopathies, progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), to support clinical development of new tau-directed therapeutic agents. METHODS: Six- and 12-month changes in regional MRI volumes and PSP Rating Scale scores were examined in 55 patients with PSP and 33 patients with CBS (78% amyloid PET negative) compared to 30 normal controls from a multicenter natural history study...
October 14, 2016: Neurology
Ryuichi Harada, Shozo Furumoto, Tetsuro Tago, Katsutoshi Furukawa, Aiko Ishiki, Naoki Tomita, Ren Iwata, Manabu Tashiro, Hiroyuki Arai, Kazuhiko Yanai, Yukitsuka Kudo, Nobuyuki Okamura
No abstract text is available yet for this article.
October 13, 2016: European Journal of Nuclear Medicine and Molecular Imaging
Ruben Smith, Martin Schain, Christer Nilsson, Olof Strandberg, Tomas Olsson, Douglas Hägerström, Jonas Jögi, Edilio Borroni, Michael Schöll, Michael Honer, Oskar Hansson
BACKGROUND: Progressive supranuclear palsy (PSP) is difficult to diagnose accurately. The recently developed tau PET tracers may improve the diagnostic work-up of PSP. METHODS: Regional tau accumulation was studied using (18) F-AV-1451 PET in 11 patients with PSP and 11 age-matched healthy controls in the Swedish BioFinder study. RESULTS: (18) F-AV-1451 standard uptake volume ratios were significantly higher in the basal ganglia in PSP patients when compared with controls (globus pallidus 1...
October 6, 2016: Movement Disorders: Official Journal of the Movement Disorder Society
Clifford R Jack, Heather J Wiste, Stephen D Weigand, Terry M Therneau, Val J Lowe, David S Knopman, Jeffrey L Gunter, Matthew L Senjem, David T Jones, Kejal Kantarci, Mary M Machulda, Michelle M Mielke, Rosebud O Roberts, Prashanthi Vemuri, Denise Reyes, Ronald C Petersen
INTRODUCTION: Our goal was to develop cut points for amyloid positron emission tomography (PET), tau PET, flouro-deoxyglucose (FDG) PET, and MRI cortical thickness. METHODS: We examined five methods for determining cut points. RESULTS: The reliable worsening method produced a cut point only for amyloid PET. The specificity, sensitivity, and accuracy of clinically impaired versus young clinically normal (CN) methods labeled the most people abnormal and all gave similar cut points for tau PET, FDG PET, and cortical thickness...
September 30, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Niklas Mattsson, Henrik Zetterberg, Shorena Janelidze, Philip S Insel, Ulf Andreasson, Erik Stomrud, Sebastian Palmqvist, David Baker, Cristina A Tan Hehir, Andreas Jeromin, David Hanlon, Linan Song, Leslie M Shaw, John Q Trojanowski, Michael W Weiner, Oskar Hansson, Kaj Blennow
OBJECTIVE: To test whether plasma tau is altered in Alzheimer disease (AD) and whether it is related to changes in cognition, CSF biomarkers of AD pathology (including β-amyloid [Aβ] and tau), brain atrophy, and brain metabolism. METHODS: This was a study of plasma tau in prospectively followed patients with AD (n = 179), patients with mild cognitive impairment (n = 195), and cognitive healthy controls (n = 189) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and cross-sectionally studied patients with AD (n = 61), mild cognitive impairment (n = 212), and subjective cognitive decline (n = 174) and controls (n = 274) from the Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably (BioFINDER) study at Lund University, Sweden...
September 30, 2016: Neurology
Laure Saint-Aubert, Ove Almkvist, Konstantinos Chiotis, Rita Almeida, Anders Wall, Agneta Nordberg
BACKGROUND: The recent development of tau-specific positron emission tomography (PET) tracers has allowed in vivo quantification of regional tau deposition and offers the opportunity to monitor the progression of tau pathology along with cognitive impairment. In this study, we investigated the relationships of cerebral tau deposition ([(18)F]THK5317-PET) and metabolism ([(18)F]FDG-PET) with concomitant cognitive function in patients with probable Alzheimer's disease (AD). METHODS: Nine patients diagnosed with AD dementia and 11 with prodromal AD (mild cognitive impairment, amyloid-positive on [(11)C]PiB-PET) were included in this study...
September 29, 2016: Alzheimer's Research & Therapy
D L Dickstein, M Y Pullman, C Fernandez, J A Short, L Kostakoglu, K Knesaurek, L Soleimani, B D Jordan, W A Gordon, K Dams-O'Connor, B N Delman, E Wong, C Y Tang, S T DeKosky, J R Stone, R C Cantu, M Sano, P R Hof, S Gandy
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder most commonly associated with repetitive traumatic brain injury (TBI) and characterized by the presence of neurofibrillary tangles of tau protein, known as a tauopathy. Currently, the diagnosis of CTE can only be definitively established postmortem. However, a new positron emission tomography (PET) ligand, [(18)F]T807/AV1451, may provide the antemortem detection of tau aggregates, and thus various tauopathies, including CTE. Our goal was to examine [(18)F]T807/AV1451 retention in athletes with neuropsychiatric symptoms associated with a history of multiple concussions...
2016: Translational Psychiatry
Dustin Wooten, Nicolas J Guehl, Eline E Verwer, Timothy M Shoup, Daniel L Yokell, Nevena Zubcevik, Neil Vasdev, Ross D Zafonte, Keith A Johnson, Georges El Fakhri, Marc David Normandin
: [(18)F]T807 is a PET radiotracer developed for imaging tau protein aggregates, which are implicated in neurological disorders including Alzheimer's disease (AD) and traumatic brain injury (TBI). The current study characterizes [(18)F]T807 pharmacokinetics in human subjects using dynamic PET imaging and metabolite-corrected arterial input functions. METHODS: Nine subjects (4 control, 3 with history of TBI, 2 mild cognitive impairment (MCI) due to suspected AD) underwent dynamic PET imaging for up to 120 minutes after bolus injection of [(18)F]T807 with arterial blood sampling...
September 22, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Courtney T Jollymore-Hughes, Ian R Pottie, Earl Martin, Terrone L Rosenberry, Sultan Darvesh
Association of cholinesterase with β-amyloid plaques and tau neurofibrillary tangles in Alzheimer's disease offers an opportunity to detect disease pathology during life. Achieving this requires development of radiolabelled cholinesterase ligands with high enzyme affinity. Various fluorinated acetophenone derivatives bind to acetylcholinesterase with high affinity, including 2,2,2-trifluoro-1-(3-dimethylaminophenyl)ethanone (1) and 1-(3-tert-butylphenyl)-2,2,2-trifluoroethanone (2). Such compounds also offer potential for incorporation of radioactive fluorine ((18)F) for Positron Emission Tomography (PET) imaging of cholinesterases in association with Alzheimer's disease pathology in the living brain...
November 1, 2016: Bioorganic & Medicinal Chemistry
Annie M Racine, Lindsay R Clark, Sara E Berman, Rebecca L Koscik, Kimberly D Mueller, Derek Norton, Christopher R Nicholas, Kaj Blennow, Henrik Zetterberg, Bruno Jedynak, Murat Bilgel, Cynthia M Carlsson, Bradley T Christian, Sanjay Asthana, Sterling C Johnson
It is not known whether computerized cognitive assessments, like the CogState battery, are sensitive to preclinical cognitive changes or pathology in people at risk for Alzheimer's disease(AD). In 469 late middle-aged participants from the Wisconsin Registry for Alzheimer's Prevention(mean age 63.8±7 years at testing; 67% female; 39% APOE4+), we examined relationships between a CogState abbreviated battery(CAB) of seven tests and demographic characteristics, traditional paper-based neuropsychological tests as well as a composite cognitive impairment index, cognitive impairment status(determined by consensus review), and biomarkers for amyloid and tau(CSF phosphorylated-tau/Aβ42 and global PET-PiB burden) and neural injury(CSF neurofilament light protein)...
October 18, 2016: Journal of Alzheimer's Disease: JAD
Suzanne L Baker, Samuel N Lockhart, Julie C Price, Mark He, Ronald H Huesman, Daniel Schonhaut, Jamie Faria, Gil Rabinovici, William J Jagust
: The goal of this paper was to evaluate the in vivo kinetics of the novel tau-specific Positron Emission Tomography (PET) radioligand, (18)F-AV-1451, in cognitively normal healthy control and Alzheimer's disease (AD) subjects, using reference region analyses. METHODS: (18)F-AV-1451 PET imaging was performed on 43 subjects (5 young healthy controls, yHCs, 23 older healthy controls, HCs, and 15 ADs). Data were collected from 0-150 min post-injection, with a break from 100-120 min...
September 1, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Philip S J Weston, Ross W Paterson, John Dickson, Anna Barnes, Jamshed B Bomanji, Irfan Kayani, Michael P Lunn, Catherine J Mummery, Jason D Warren, Martin N Rossor, Nick C Fox, Henrik Zetterberg, Jonathan M Schott
Cerebrospinal fluid (CSF) measures of amyloid and tau are the first-line Alzheimer's disease biomarkers in many clinical centers. We assessed if and when the addition of amyloid PET following CSF measurements provides added diagnostic value. Twenty patients from a cognitive clinic, who had undergone detailed assessment including CSF measures, went on to have amyloid PET. The treating neurologist's working diagnosis, and degree of diagnostic certainty, was assessed both before and after the PET. Amyloid PET changed the diagnosis in 7/20 cases...
October 18, 2016: Journal of Alzheimer's Disease: JAD
Cyrus A Raji, David A Merrill, Jorge R Barrio, Bennet Omalu, Gary W Small
Here a case is presented of a 51-year-old former high school football player with multiple concussions, including one episode with loss of consciousness. The patient experienced 6 years of cognitive and mood decline, and his wife corroborated increasing memory loss, attentional difficulties, and depressed mood without suicidal ideation. He had been unable to maintain full-time employment because of progressive decline. Based on his presentation, he had been previously diagnosed with attention deficit hyperactivity disorder and bipolar disorder, type II...
October 2016: American Journal of Geriatric Psychiatry
Brian A Gordon, Tyler Blazey, Yi Su, Anne M Fagan, David M Holtzman, John C Morris, Tammie L S Benzinger
Importance: Preclinical Alzheimer disease (AD) can be staged using a 2-factor model denoting the presence or absence of β-amyloid (Aβ+/-) and neurodegeneration (ND+/-). The association of these stages with longitudinal biomarker outcomes is unknown. Objective: To examine whether longitudinal Aβ accumulation and hippocampal atrophy differ based on initial preclinical staging. Design, Setting, and Participants: This longitudinal population-based cohort study used data collected at the Knight Alzheimer Disease Research Center, Washington University, St Louis, Missouri, from December 1, 2006, to June 31, 2015...
October 1, 2016: JAMA Neurology
Yanyan Kong, Yihui Guan, Fengchun Hua, Zhengwei Zhang, Xiuhong Lu, Tengfang Zhu, Bizeng Zhao, Jianhua Zhu, Cong Li, Jian Chen
The quantification of neurofibrillary tangles (NFTs) using specific PET tracers can facilitate the diagnosis of Alzheimer's disease (AD) and allow monitoring of disease progression and treatment efficacy. [(18)F]-THK523 has shown high affinity and selectivity for tau pathology. However, its high retention in white matter, which makes simple visual inspection difficult, may limit its use in research or clinical settings. In this paper, we optimized the automated radiosynthesis of [(11)C]-TKF and evaluated its biodistribution and toxicity in C57 mice...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Sonja Schönecker, Matthias Brendel, Marion Huber, Christian Vollmar, Hans-Juergen Huppertz, Stefan Teipel, Nobuyuki Okamura, Johannes Levin, Axel Rominger, Adrian Danek
BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia in the elderly. The possibility of disease-modifying strategies has evoked a need for early and accurate diagnosis. To improve the accuracy of the clinical diagnosis of AD, biomarkers like cerebrospinal fluid (CSF) and neuroimaging techniques like magnetic resonance imaging (MRI) and positron emission tomography (PET) have been incorporated into the diagnostic guidelines of AD. CASE PRESENTATION: In this case report we outline in reference to one of our patients with presenile dementia the current approaches to the diagnosis of AD...
2016: BMC Neurology
Rizwan S Akhtar, Sharon X Xie, Laura Brennan, Michael J Pontecorvo, Howard I Hurtig, John Q Trojanowski, Daniel Weintraub, Andrew D Siderowf
BACKGROUND: Neuronal loss and α-synuclein (α-syn) pathology are diagnostic of PD in the appropriate clinical context. However, some PD patients have co-morbid Alzheimer's disease (AD) pathology on autopsy, including amyloid-β (Aβ) plaques and neurofibrillary tangles. Florbetapir((18)F) is a PET ligand that detects Aβ pathology. We hypothesized that florbetapir((18)F) imaging could detect Aβ pathology in Parkinson disease dementia (PDD) patients prior to death. OBJECTIVE: To determine the utility of florbetapir((18)F) PET imaging in detecting Aβ pathology in patients with autopsy-confirmed PDD...
July 2016: Movement Disorders Clinical Practice
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