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Jolien Schaeverbeke, Benjamin Gille, Katarzyna Adamczuk, Hugo Vanderstichele, Emeric Chassaing, Rose Bruffaerts, Veerle Neyens, Erik Stoops, Jos Tournoy, Rik Vandenberghe, Koen Poesen
The main pathophysiological alterations of Alzheimer's disease (AD) include loss of neuronal and synaptic integrity, amyloidogenic processing and neuroinflammation. Similar alterations can, however, also be observed in cognitively intact older subjects and may prelude the clinical manifestation of AD. The objectives of this prospective cross-sectional study in a cohort of 38 cognitively intact older adults were twofold: (i) to investigate the latent relationship among cerebrospinal fluid (CSF) biomarkers reflecting the main pathophysiological processes of AD, and (ii) to assess the correlation between these biomarkers and gray matter volume as well as amyloid load...
February 5, 2019: Journal of Neurochemistry
Maurizio Gallucci, Carola Dell'Acqua, Cristina Bergamelli, Chiara Fenoglio, Maria Serpente, Daniela Galimberti, Vittorio Fiore, Stefano Medea, Michele Gregianin, Maria Elena Di Battista
We report the case of a woman firstly referred to our Memory Clinic at the age of 61, following the development of cognitive complaints and difficulties in sustained attention. The investigation that was performed showed: predominant executive dysfunctions at the neuropsychological evaluation, with mild, partial and stable involvement of the memory domain; cortical and subcortical atrophy with well-preserved hippocampal structures at MRI; marked fronto-temporal and moderate parietal hypometabolism from 18F-FDG PET study with a sparing of the posterior cingulate and precuneus; positivity of amyloid-β at 18F-Flutemetamol PET; an hexanucleotide intermediate repeats expansion of C9ORF72 gene (12//38 repeats) and ApoE genotype ɛ4/ɛ4...
January 28, 2019: Journal of Alzheimer's Disease: JAD
Kevin Duff, Kevin P Horn, John M Hoffman
PURPOSE: Longitudinal studies into the variability of F-Flutemetamol uptake are lacking. METHODS/PATIENTS: Therefore, the current study examined change in F-Flutemetamol uptake in 19 nondemented older adults (65 to 82 y old) who were either cognitively intact or had Mild Cognitive Impairment (MCI) who were scanned twice across 3.6 years. RESULTS: Baseline and follow-up composite SUVRs were significantly correlated (0.96, P<0.001). Significant increases in the composite SUVR from baseline to follow-up were observed (P=0...
January 8, 2019: Alzheimer Disease and Associated Disorders
Rik Ossenkoppele, Ruben Smith, Tomas Ohlsson, Olof Strandberg, Niklas Mattsson, Philip S Insel, Sebastian Palmqvist, Oskar Hansson
OBJECTIVE: To examine the cross-sectional associations between regional tau, β-amyloid (Aβ), and cortical thickness and neuropsychological function across the preclinical and clinical spectrum of Alzheimer disease (AD). METHODS: We included 106 participants from the Swedish Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably (BioFINDER) study, of whom 33 had preclinical AD (Aβ-positive cognitively normal individuals), 25 had prodromal AD (Aβ-positive mild cognitive impairment), and 48 had probable AD dementia...
February 5, 2019: Neurology
Yu Yan, Edward Somer, Vicente Grau
BACKGROUND: New PET tracers could have a substantial impact on the early diagnosis of Alzheimer's disease (AD), particularly if they are accompanied by optimised image analysis and machine learning methods. Fractal dimension (FD) analysis, a measure of shape complexity, has been proven useful in MRI but its application to fluorine-18 amyloid PET has not yet been demonstrated. Shannon entropy (SE) has also been proposed as a measure of image complexity in DTI imaging, but it is not yet widely used in radiology...
November 29, 2018: Nuclear Medicine Communications
Lyduine Collij, Elles Konijnenberg, Juhan Reimand, Mara Ten Kate, Anouk Den Braber, Isadora Lopes Alves, Marissa Zwan, Maqsood Yaqub, Daniëlle Van Assema, Alle Meije Wink, Adriaan Lammertsma, Philip Scheltens, Pieter Jelle Visser, Frederik Barkhof, Bart Van Berckel
Objective: Determine the optimal approach for assessing amyloid pathology in a cognitively normal elderly population. Methods: Dynamic [18 F]flutemetamol PET scans acquired using a coffee-break protocol (0-30 and 90-110 min. scan) from 190 cognitively normal elderly (mean age 70.4 years, 60% female) were included. Parametric images were generated from standard uptake value ratio (SUVr) and non-displaceable binding potential (BPND ) methods, with cerebellar grey matter as a reference region and were visually assessed by three trained readers...
October 12, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Luca Filippi, Agostino Chiaravalloti, Oreste Bagni, Orazio Schillaci
Alzheimer's disease (AD) is the most common cause of dementia in the elderly, with tremendous impact on the affected individuals and the society. Definitive diagnosis can be achieved only by post mortem examination. Clinical diagnosis criteria currently applied in clinical practice for AD often fail to accurately discriminate between AD and non-AD dementia with up to 40% of misdiagnosed patients. Several published papers demonstrated that the pre-clinical phase of AD is characterized by an early rise in beta-amyloid accumulation into inter-neuronal space, followed by a severe synaptic dysfunction...
2018: American Journal of Nuclear Medicine and Molecular Imaging
Lee Josephson, Nancy Stratman, YuTing Liu, Fang Qian, Steven H Liang, Neil Vasdev, Shil Patel
Development of an α-synuclein (α-Syn) positron emission tomography agent for the diagnosis and evaluation of Parkinson disease therapy is a key goal of neurodegenerative disease research. BF-227 has been described as an α-Syn binder and hence was employed as a lead to generate a library of α-Syn-binding compounds. [3 H]BF-227 bound to α-Syn and amyloid β peptide (Aβ) fibrils with affinities (KD ) of 46.0 nM and 15.7 nM, respectively. Affinities of BF-227-like compounds (expressed as Ki ) for α-Syn and Aβ fibrils were determined, along with 5 reference compounds (flutafuranol, flutemetamol, florbetapir, BF-227, and PiB)...
January 2018: Molecular Imaging
Otakar Belohlavek, Monika Jaruskova, Magdalena Skopalova, Gabriela Szarazova, Katerina Simonova
PURPOSE: We investigated whether the reproducibility of standard visual reporting (STD method) in flutemetamol (FMM) PET can be improved using a newly introduced method that uses grey matter edges derived from the perfusion phase (GM-EDGE method). METHODS: Two-phase FMM PET was performed in 121 patients with mild cognitive impairment. Five nuclear medicine physicians blindly and independently evaluated all late-phase scans, initially employing the STD method and later the GM-EDGE method...
August 29, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Pierrick Bourgeat, Vincent Doré, Jurgen Fripp, David Ames, Colin L Masters, Olivier Salvado, Victor L Villemagne, Christopher C Rowe
The centiloid scale was recently proposed to provide a standard framework for the quantification of β-amyloid PET images, so that amyloid burden can be expressed on a standard scale. While the framework prescribes SPM8 as the standard analysis method for PET quantification, non-standard methods can be calibrated to produce centiloid values. We have previously developed a PET-only quantification: CapAIBL. In this study, we show how CapAIBL can be calibrated to the centiloid scale. METHODS: Calibration images for 11 C-PiB, 18 F-NAV4694, 18 F-Florbetaben, 18 F-Flutemetamol and 18 F- Florbetapir were analysed using the standard method and CapAIBL...
August 18, 2018: NeuroImage
Dietmar Rudolf Thal, Thomas G Beach, Michelle Zanette, Johan Lilja, Kerstin Heurling, Aruna Chakrabarty, Azzam Ismail, Gill Farrar, Christopher Buckley, Adrian P L Smith
The deposition of the amyloid β-protein (Aβ) in senile plaques is one of the histopathological hallmarks of Alzheimer's disease (AD). Aβ-plaques arise first in neocortical areas and, then, expand into further brain regions in a process described by 5 phases. Since it is possible to identify amyloid pathology with radioactive-labeled tracers by positron emission tomography (PET) the question arises whether it is possible to distinguish the neuropathological Aβ-phases with amyloid PET imaging. To address this question we reassessed 97 cases of the end-of-life study cohort of the phase 3 [18 F]flutemetamol trial (ClinicalTrials...
October 2018: Acta Neuropathologica
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...
September 1, 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...
September 1, 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
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