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G S M Sundaram, Kristen Binz, Vedica Sharma, Melany Yeung, Vijay Sharma
Thioflavin T (ThT), a positively charged heterocyclic small molecule, is a widely used fluorescent marker of amyloid pathophysiology to confirm the cause of death in post mortem brain tissue of Alzheimer's disease (AD) patients. Literature precedents indicate that current positron emission tomography (PET) agents, such as 11 C-PIB and 18 F-flutemetamol, share significant structural similarity with ThT, a lipophilic dye which does not traverse the blood-brain barrier (BBB) to enable the detection of Aβ plaques in vivo ...
June 1, 2018: MedChemComm
Niklas Mattsson, Oscar Eriksson, Olof Lindberg, Michael Schöll, Björn Lampinen, Markus Nilsson, Philip S Insel, Ronald Lautner, Olof Strandberg, Danielle van Westen, Henrik Zetterberg, Kaj Blennow, Sebastian Palmqvist, Erik Stomrud, Oskar Hansson
Apolipoprotein (APOE) ε4 is a major genetic risk factor for Alzheimer's disease (AD), but its importance for the clinical and biological heterogeneity in AD is unclear, particularly at the prodromal stage. We analyzed 151 prodromal AD patients (44 APOE ε4-negative and 107 APOE ε4-positive) from the BioFINDER study. We tested cognition, 18F-flutemetamol β-amyloid (Aβ) positron emission tomography, cerebrospinal fluid biomarkers of Aβ, tau and neurodegeneration, and magnetic resonance imaging of white matter pathology and brain structure...
July 11, 2018: Neurobiology of Aging
Elles Konijnenberg, Stephen F Carter, Mara Ten Kate, Anouk den Braber, Jori Tomassen, Chinenye Amadi, Linda Wesselman, Hoang-Ton Nguyen, Jacoba A van de Kreeke, Maqsood Yaqub, Matteo Demuru, Sandra D Mulder, Arjan Hillebrand, Femke H Bouwman, Charlotte E Teunissen, Erik H Serné, Annette C Moll, Frank D Verbraak, Rainer Hinz, Neil Pendleton, Adriaan A Lammertsma, Bart N M van Berckel, Frederik Barkhof, Dorret I Boomsma, Philip Scheltens, Karl Herholz, Pieter Jelle Visser
BACKGROUND: Amyloid pathology is the pathological hallmark in Alzheimer's disease (AD) and can precede clinical dementia by decades. So far it remains unclear how amyloid pathology leads to cognitive impairment and dementia. To design AD prevention trials it is key to include cognitively normal subjects at high risk for amyloid pathology and to find predictors of cognitive decline in these subjects. These goals can be accomplished by targeting twins, with additional benefits to identify genetic and environmental pathways for amyloid pathology, other AD biomarkers, and cognitive decline...
August 4, 2018: Alzheimer's Research & Therapy
Hye Joo Son, Young Jin Jeong, Hyun Jin Yoon, Sang Yoon Lee, Go-Eun Choi, Ji-Ae Park, Min Hwan Kim, Kyo Chul Lee, Yong Jin Lee, Mun Ki Kim, Kook Cho, Do-Young Kang
BACKGROUND: Although amyloid beta (Aβ) imaging is widely used for diagnosing and monitoring Alzheimer's disease in clinical fields, paralleling comparison between 18 F-flutemetamol and 18 F-florbetaben was rarely attempted in AD mouse model. We performed a comparison of Aβ PET images between 18 F-flutemetamol and 18 F-florbetaben in a recently developed APPswe mouse model, C57BL/6-Tg (NSE-hAPPsw) Korl. RESULTS: After an injection (0.23 mCi) of 18 F-flutemetamol and 18 F-florbetaben at a time interval of 2-3 days, we compared group difference of SUVR and kinetic parameters between the AD (n = 7) and control (n = 7) mice, as well as between 18 F-flutemetamol and 18 F-florbetaben image...
July 27, 2018: BMC Neuroscience
Melanie Dani, Melanie Wood, Ruth Mizoguchi, Zhen Fan, Zuzana Walker, Richard Morgan, Rainer Hinz, Maya Biju, Tarun Kuruvilla, David J Brooks, Paul Edison
Alzheimer's disease is characterized by the histopathological presence of amyloid-β plaques and tau-containing neurofibrillary tangles. Microglial activation is also a recognized pathological component. The relationship between microglial activation and protein aggregation is still debated. We investigated the relationship between amyloid plaques, tau tangles and activated microglia using PET imaging. Fifty-one subjects (19 healthy controls, 16 mild cognitive impairment and 16 Alzheimer's disease subjects) participated in the study...
July 20, 2018: Brain: a Journal of Neurology
Milos D Ikonomovic, Enrico R Fantoni, Gill Farrar, Stephen Salloway
BACKGROUND: The performance of [18 F]flutemetamol amyloid PET against histopathological standards of truth was the subject of our recent article in Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring (2017;9:25-34). MAIN BODY: This viewpoint article addresses infrequently observed discordance between visual [18 F]flutemetamol PET image readings and histopathology based solely on neuritic plaque assessment by CERAD criteria, which is resolved by assessing both neuritic and diffuse plaques and/or brain atrophy...
June 23, 2018: Alzheimer's Research & Therapy
Johan Lilja, Antoine Leuzy, Konstantinos Chiotis, Irina Savitcheva, Jens Sörensen, Agneta Nordberg
Though currently approved for visual assessment only, there is evidence to suggest that quantification of amyloid-β (Aβ) PET images may reduce inter-reader variability and aid in the monitoring of treatment effects in clinical trials. Quantification typically involves a regional atlas in standard space, requiring PET images to be spatially normalized. Different uptake patterns in Aβ-positive and Aβ-negative subjects, however, makes spatial normalization challenging. In this study we propose a method to spatially normalize [18 F]flutemetamol images, using a synthetic template based on principal component images to overcome these challenges...
June 14, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
David A Wolk, Carl Sadowsky, Beth Safirstein, Juha O Rinne, Ranjan Duara, Richard Perry, Marc Agronin, Jose Gamez, Jiong Shi, Adrian Ivanoiu, Lennart Minthon, Zuzana Walker, Steen Hasselbalch, Clive Holmes, Marwan Sabbagh, Marilyn Albert, Adam Fleisher, Paul Loughlin, Eric Triau, Kirk Frey, Peter Høgh, Andrea Bozoki, Roger Bullock, Eric Salmon, Gillian Farrar, Christopher J Buckley, Michelle Zanette, Paul F Sherwin, Andrea Cherubini, Fraser Inglis
Importance: Patients with amnestic mild cognitive impairment (aMCI) may progress to clinical Alzheimer disease (AD), remain stable, or revert to normal. Earlier progression to AD among patients who were β-amyloid positive vs those who were β-amyloid negative has been previously observed. Current research now accepts that a combination of biomarkers could provide greater refinement in the assessment of risk for clinical progression. Objective: To evaluate the ability of flutemetamol F 18 and other biomarkers to assess the risk of progression from aMCI to probable AD...
May 14, 2018: JAMA Neurology
Li-Ming Wang, Qi Wu, Ryan A Kirk, Kevin P Horn, Ahmed H Ebada Salem, John M Hoffman, Jeffrey T Yap, Joshua A Sonnen, Rheal A Towner, Fernando A Bozza, Rosana S Rodrigues, Kathryn A Morton
Amyloid beta (Aβ) plaques are not specific to Alzheimer's disease and occur with aging and neurodegenerative disorders. Soluble brain Aβ may be neuroprotective and increases in response to neuroinflammation. Sepsis is associated with neurocognitive compromise. The objective was to determine, in a rat endotoxemia model of sepsis, whether neuroinflammation and soluble Aβ production are associated with Aβ plaque and hyperphosphorylated tau deposition in the brain. Male Sprague Dawley rats received a single intraperitoneal injection of 10 mg/kg of lipopolysaccharide endotoxin (LPS)...
2018: American Journal of Nuclear Medicine and Molecular Imaging
J M G van Bergen, X Li, F C Quevenco, A F Gietl, V Treyer, R Meyer, A Buck, P A Kaufmann, R M Nitsch, P C M van Zijl, C Hock, P G Unschuld
The accumulation of β-amyloid plaques is a hallmark of Alzheimer's disease (AD), and recently published data suggest that increased brain iron burden may reflect pathologies that synergistically contribute to the development of cognitive dysfunction. While preclinical disease stages are considered most promising for therapeutic intervention, the link between emerging AD-pathology and earliest clinical symptoms remains largely unclear. In the current study we therefore investigated local correlations between iron and β-amyloid plaques, and their possible association with cognitive performance in healthy older adults...
July 1, 2018: NeuroImage
Zhen Fan, Melanie Dani, Grazia D Femminella, Melanie Wood, Valeria Calsolaro, Mattia Veronese, Federico Turkheimer, Steve Gentleman, David J Brooks, Rainer Hinz, Paul Edison
PURPOSE: Neuroinflammation and microglial activation play an important role in amnestic mild cognitive impairment (MCI) and Alzheimer's disease. In this study, we investigated the spatial distribution of neuroinflammation in MCI subjects, using spectral analysis (SA) to generate parametric maps and quantify 11 C-PBR28 PET, and compared these with compartmental and other kinetic models of quantification. METHODS: Thirteen MCI and nine healthy controls were enrolled in this study...
July 2018: European Journal of Nuclear Medicine and Molecular Imaging
Silvia Morbelli, Matteo Bauckneht
Amyloid plaques are a neuropathologic hallmark of Alzheimer's disease (AD), which can be imaged through positron emission tomography (PET) technology using radiopharmaceuticals that selectively bind to the fibrillar aggregates of amyloid-β plaques (Amy-PET). Several radiotracers for amyloid PET have been investigated, including 11 C-Pittsburgh compound B and the 18 F-labeled compounds such as 18 F-florbetaben, 18 F-florbetapir, and 18 F-flutemetamol. Besides the injected radiotracer, images can be interpreted by means of visual/qualitative, semiquantitative, and quantitative criteria...
2018: Methods in Molecular Biology
Lisa Flem Kalheim, Tormod Fladby, Christopher Coello, Atle Bjørnerud, Per Selnes
Flutemetamol (18F-Flut) is an [18F]-labelled amyloid PET tracer with increasing availability. The main objectives of this study were to investigate 1) cerebrospinal fluid (CSF) Aβ 1-42 (Aβ42) concentrations associated with regional 18F-Flut uptake, 2) associations between cortical 18F-Flut and [18F]-fludeoxyglucose (18F-FDG)-PET, and 3) the potential use of 18F-Flut in WM pathology. Cognitively impaired, nondemented subjects were recruited (n = 44). CSF was drawn, and 18F-Flut-PET, 18F-FDG-PET, and MRI performed...
2018: Journal of Alzheimer's Disease: JAD
Oskar Hansson, John Seibyl, Erik Stomrud, Henrik Zetterberg, John Q Trojanowski, Tobias Bittner, Valeria Lifke, Veronika Corradini, Udo Eichenlaub, Richard Batrla, Katharina Buck, Katharina Zink, Christina Rabe, Kaj Blennow, Leslie M Shaw
INTRODUCTION: We studied whether fully automated Elecsys cerebrospinal fluid (CSF) immunoassay results were concordant with positron emission tomography (PET) and predicted clinical progression, even with cutoffs established in an independent cohort. METHODS: Cutoffs for Elecsys amyloid-β1-42 (Aβ), total tau/Aβ(1-42), and phosphorylated tau/Aβ(1-42) were defined against [18 F]flutemetamol PET in Swedish BioFINDER (n = 277) and validated against [18 F]florbetapir PET in Alzheimer's Disease Neuroimaging Initiative (n = 646)...
March 1, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Jamie Moreland, Timo Urhemaa, Mark van Gils, Jyrki Lötjönen, Jan Wolber, Christopher J Buckley
OBJECTIVE: The objective of this study was to develop and validate a practical computerized prognostic model that uses baseline psychometric and imaging data, including results of PET imaging of amyloid deposition, to predict the progression to dementia in patients at risk for Alzheimer's disease (AD). PATIENTS AND METHODS: Data from patients in a phase II trial of [F]flutemetamol for PET imaging of brain amyloid and from the Alzheimer's Disease Neuroimaging Initiative were used to train the prognostic model to yield a disease state index (DSI), a measure of the similarity of an individual patient's data to data from patients in specific diagnostic groups...
April 2018: Nuclear Medicine Communications
Jiri M G van Bergen, Xu Li, Frances C Quevenco, Anton F Gietl, Valerie Treyer, Sandra E Leh, Rafael Meyer, Alfred Buck, Philipp A Kaufmann, Roger M Nitsch, Peter C M van Zijl, Christoph Hock, Paul G Unschuld
The aging brain is characterized by an increased presence of neurodegenerative and vascular pathologies. However, there is substantial variation regarding the relationship between an individual's pathological burden and resulting cognitive impairment. To identify correlates of preserved cognitive functioning at highest age, the relationship between β-amyloid plaque load, presence of small vessel cerebrovascular disease (SVCD), iron-burden, and brain atrophy was investigated. Eighty cognitively unimpaired participants (44 oldest-old, aged 85-96 years; 36 younger-old, aged 55-80 years) were scanned by integrated positron emission tomography-magnetic resonance imaging for assessing beta regional amyloid plaque load (18F-flutemetamol), white matter hyperintensities as an indicator of SVCD (fluid-attenuated inversion recovery-magnetic resonance imaging), and iron load (quantitative susceptibility mapping)...
April 2018: Neurobiology of Aging
Katarina Nägga, Anna-Märta Gustavsson, Erik Stomrud, Daniel Lindqvist, Danielle van Westen, Kaj Blennow, Henrik Zetterberg, Olle Melander, Oskar Hansson
OBJECTIVE: To evaluate the effect of midlife lipid levels on Alzheimer brain pathology 20 years later in cognitively normal elderly individuals. METHODS: This is a longitudinal cohort study of 318 cognitively normal individuals with data on fasting lipid levels at midlife (mean age 54 years). Presence of β-amyloid (Aβ) and tau pathologies 20 years later (mean age 73 years) were detected by quantifying Alzheimer disease (AD) biomarkers in CSF. In a subset (n = 134), Aβ (18 F-flutemetamol) PET was also performed...
January 2, 2018: Neurology
Gabriel Martínez, Robin Wm Vernooij, Paulina Fuentes Padilla, Javier Zamora, Leon Flicker, Xavier Bonfill Cosp
BACKGROUND: 18 F-flutemetamol uptake by brain tissue, measured by positron emission tomography (PET), is accepted by regulatory agencies like the Food and Drug Administration (FDA) and the European Medicine Agencies (EMA) for assessing amyloid load in people with dementia. Its added value is mainly demonstrated by excluding Alzheimer's pathology in an established dementia diagnosis. However, the National Institute on Aging and Alzheimer's Association (NIA-AA) revised the diagnostic criteria for Alzheimer's disease and the confidence in the diagnosis of mild cognitive impairment (MCI) due to Alzheimer's disease may be increased when using some amyloid biomarkers tests like 18 F-flutemetamol...
November 22, 2017: Cochrane Database of Systematic Reviews
Shorena Janelidze, Josef Pannee, Alvydas Mikulskis, Ping Chiao, Henrik Zetterberg, Kaj Blennow, Oskar Hansson
Importance: Visual assessment of amyloid positron emission tomographic (PET) images has been approved by regulatory authorities for clinical use. Several immunoassays have been developed to measure β-amyloid (Aβ) 42 in cerebrospinal fluid (CSF). The agreement between CSF Aβ42 measures from different immunoassays and visual PET readings may influence the use of CSF biomarkers and/or amyloid PET assessment in clinical practice and trials. Objective: To determine the concordance between CSF Aβ42 levels measured using 5 different immunoassays and visual amyloid PET analysis...
December 1, 2017: JAMA Neurology
Elena Rolandi, Enrica Cavedo, Michela Pievani, Samantha Galluzzi, Federica Ribaldi, Christopher Buckley, Colm Cunningham, Ugo Paolo Guerra, Monica Musarra, Sabrina Morzenti, Silvia Magnaldi, Mirko Patassini, Flavio Terragnoli, Luca Matascioli, Simone Franzoni, Giorgio Annoni, Lucio Carnevali, Giuseppe Bellelli, Giovanni B Frisoni
The aim of the study was to investigate the association between postoperative delirium (POD) and in vivo markers of Alzheimer's disease pathology in nondemented hip fracture surgery patients. POD was assessed with the Confusion Assessment Method. Amyloid load was quantified on 18 F-Flutemetamol positron emission tomography images as standardized uptake value ratio. Secondary outcome measures were gray matter volumes, white matter integrity, and functional connectivity at rest. All the patients with POD (POD+, N = 5) were amyloid negative (standardized uptake value ratio <0...
January 2018: Neurobiology of Aging
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