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Amyloid and Tau Positron Emission Tomography Imaging in Alzheimer's Disease and Other Tauopathies

FRONTIERS IN AGING NEUROSCIENCE (2022)

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Review Clinical Neurology

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Summary: Neurological symptoms depend on the lesions' location in the nervous system, highlighting the importance of brain imaging for neurologists. Treatment, on the other hand, depends on the biological nature of the lesions. Developing radiotracers specific for proteinopathies in neurodegenerative disorders is crucial for understanding the relationships between pathology, clinical symptoms, and therapeutic interventions.

ACTA NEUROLOGICA BELGICA (2022)

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Article Clinical Neurology

18F-MK-6240 tau-PET in genetic frontotemporal dementia

Jake P. Levy et al.

Summary: This study demonstrates promising potential for F-18-MK-6240 PET tracer in detecting tau in genetic frontotemporal dementia, with significant binding in P301L and R406W MAPT mutation subjects and no non-specific binding observed. The results suggest that a positive F-18-MK-6240 tau-PET does not necessarily indicate Alzheimer's disease diagnosis and may have applications in tauopathies beyond Alzheimer's.

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Article Clinical Neurology

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Eric E. Abrahamson et al.

Summary: In a post-mortem study, it has been found that the amyloid PET radioligand Pittsburgh compound B (PiB) interacts poorly with cotton wool plaques, which are common in familial Alzheimer's disease but rare in sporadic Alzheimer's disease. This limited interaction may lead to an underestimation of total amyloid burden in patients with familial Alzheimer's disease.

BRAIN (2022)

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Patterns of Distribution of F-18-THK5351 Positron Emission Tomography in Alzheimer's Disease Continuum

Takashi Nihashi et al.

Summary: Using the F-18-THK5351 tracer, the study investigated the changes in accumulation patterns in individuals along the Alzheimer's disease continuum. The results showed an increase in F-18-THK5351 accumulation with disease progression, suggesting its potential as a tool for visualizing the severity of Alzheimer's disease.

JOURNAL OF ALZHEIMERS DISEASE (2022)

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In Vivo 18F-Flortaucipir PET Does Not Accurately Support the Staging of Progressive Supranuclear Palsy

Maura Malpetti et al.

Summary: The study found that F-18-flortaucipir PET does not correspond to neuropathologic staging in PSP. The analytic approach seeking to mirror in vivo neuropathology staging with PET-to-autopsy correlational analyses might enable in vivo staging with next-generation tau PET tracers; however, further evidence and comparisons with postmortem data are needed.

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Review Multidisciplinary Sciences

Cryo-EM structures of amyloid-b 42 filaments from human brains

Yang Yang et al.

Summary: Filament assembly of A beta 42 peptides is a central event in Alzheimer's disease. This study provides cryo-EM structures of A beta 42 filaments from human brains, revealing two types of structurally related filaments. Understanding the structures of A beta 42 filaments from human brains may have important implications for the development of assembly inhibitors and improved imaging agents.

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Advances and controversies in frontotemporal dementia: diagnosis, biomarkers, and therapeutic considerations

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Summary: Frontotemporal dementia is a clinical syndrome characterized by progressive changes in behavior, executive function, or language. Frontotemporal lobar degeneration encompasses the neurodegenerative diseases associated with these clinical syndromes and involves proteinopathies related to frontotemporal network dysfunction. Advances in clinical, genetic, and molecular characterization have provided new insights into the broader range of signs and symptoms associated with frontotemporal dementia. Accurate and early diagnosis is now possible due to the development of neuropsychological measures focusing on social cognition. Plasma and CSF biomarkers, as well as structural and functional imaging, will be useful for future clinical trials in frontotemporal dementia.

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Amyloid, tau, and astrocyte pathology in autosomal-dominant Alzheimer's disease variants: AβPParc and PSEN1DE9

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Summary: This study demonstrates differences in the properties of amyloid plaques between two genetic variants of AD and sAD. Despite the lack of measurable amyloid fibrils in AβPP mutation carriers, high regional tau and astrocyte binding were observed. Differences in the pathological cascade between AD variants were suggested, warranting further exploration in vivo.

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[18F]THK5317 imaging as a tool for predicting prospective cognitive decline in Alzheimer's disease

Konstantinos Chiotis et al.

Summary: This study suggests that baseline [F-18]THK5317 binding in temporal areas is accurate in predicting future cognitive decline in patients with AD spectrum, and is strongly associated with the rate of cognitive decline. Other baseline biomarkers were less accurate in prediction and not associated with the rate of cognitive decline.

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Mona-Lisa Malarte et al.

Summary: MK6240 is a second-generation tau PET tracer designed to detect neurofibrillary tangles in the brains of Alzheimer's disease patients, showing high binding affinity. Results of the study indicate that it has different binding characteristics from first-generation tau PET tracers, demonstrating the complexity of tau tracer binding with various affinities for different binding sites.

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Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?

Fangda Leng et al.

Summary: Microglial activation and neuroinflammation play important roles in Alzheimer's disease, affecting disease progression and pathologies. Current research focuses on the interplay between neuroinflammation and amyloid and tau pathologies, with a specific interest in modulating microglia as a therapeutic strategy for AD.

NATURE REVIEWS NEUROLOGY (2021)

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High-Contrast In Vivo Imaging of Tau Pathologies in Alzheimer's and Non-Alzheimer's Disease Tauopathies

Kenji Tagai et al.

Summary: A panel of radiochemicals for in vivo PET imaging of tau pathologies in AD has been developed, but sensitive detection of FTLD tau inclusions remains challenging. The imaging probe PM-PBB3 successfully captures diverse tau deposits in AD and FTLD, with increased binding observed in diseased patients in a subsequent clinical PET study. Visual inspection of F-18-PM-PBB3-PET images aids in individually based identification of diverse clinical phenotypes of FTLD on a neuropathological basis.

NEURON (2021)

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Longitudinal amyloid and tau accumulation in autosomal dominant Alzheimer's disease: findings from the Colombia-Boston (COLBOS) biomarker study

Justin S. Sanchez et al.

Summary: In ADAD, there are different rates of tau accumulation in various brain regions, with the fastest accumulation in the parietal neocortex. The baseline EC tau PET signal is a significant predictor of subsequent neocortical tau accumulation and cognitive decline within carriers.

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Yang Shi et al.

Summary: The structures of tau filaments from different tauopathies vary, allowing for a hierarchical classification of these diseases. Some tauopathies share similar filament folds, while others have distinct folding patterns.

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Philip Scheltens et al.

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Associations of Plasma Phospho-Tau217 Levels With Tau Positron Emission Tomography in Early Alzheimer Disease

Shorena Janelidze et al.

Summary: This study highlights the potential of plasma P-tau217 as an early biomarker for Alzheimer's disease, showing elevated levels before tau-PET detected insoluble tau aggregates. Modeling suggests that changes in plasma and CSF P-tau217 precede tau-PET signals, indicating its usefulness in detecting early AD brain pathology.

JAMA NEUROLOGY (2021)

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Baseline [18F]GTP1 tau PET imaging is associated with subsequent cognitive decline in Alzheimer's disease

Edmond Teng et al.

Summary: This study evaluated the relationship between tau PET imaging and subsequent cognitive decline in Alzheimer's disease. The results indicated that higher baseline tau PET signal was associated with faster rates of cognitive decline. Tau PET imaging may be useful for identifying AD patients at risk for more rapid cognitive decline.

ALZHEIMERS RESEARCH & THERAPY (2021)

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Cryo-EM structures of tau filaments from Alzheimer's disease with PET ligand APN-1607

Yang Shi et al.

Summary: A newly described PET ligand, APN-1607, was found to bind to specific sites in the Alzheimer's disease fold, potentially leading to the development of new ligands with increased specificity and binding activity. Additionally, tau filaments from posterior cortical atrophy (PCA) and primary age-related tauopathy (PART) were shown to be identical to those from AD.

ACTA NEUROPATHOLOGICA (2021)

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18F-THK5351 Positron Emission Tomography Imaging in Neurodegenerative Tauopathies

Michinori Ezura et al.

Summary: In vivo tau deposits and MAO-B density detection using F-18-THK5351 PET may assist in the differential diagnosis of tauopathies and understanding disease stages. Regional F-18-THK5351 retention is associated with cognitive function in patients with CBS and PSP.

FRONTIERS IN AGING NEUROSCIENCE (2021)

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The Alzheimer's Association international guidelines for handling of cerebrospinal fluid for routine clinical measurements of amyloid β and tau

Oskar Hansson et al.

Summary: To address variability in measurements across laboratories, a workgroup led by the Alzheimer's Association developed a simplified and standardized pre-analytical protocol for CSF collection and handling, aiming to improve AD diagnostic accuracy and reduce patient misclassification rates.

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Discriminatory ability of next-generation tau PET tracers for Alzheimer's disease

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Summary: A new generation of tau PET tracers has been developed for the imaging of Alzheimer's disease and other dementias with high specificity, showing potential to differentiate Alzheimer's disease from other dementias in clinical applications. Despite some remaining challenges, these new tracers have the potential to play an important role in clinical practice.

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Georg Meisl et al.

Summary: The study reveals that limiting local replication may constitute the most promising strategy to control tau accumulation in Alzheimer's disease, starting from Braak stage III.

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Summary: The use of multi-imaging tracers revealed different regional pattern of changes in autopsy AD brain with respect to amyloid plaque pathology versus astrogliosis and microgliosis, showing certain positive correlations between them.

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Four distinct trajectories of tau deposition identified in Alzheimer's disease

Jacob W. Vogel et al.

Summary: By using an unbiased subtyping algorithm, the study systematically characterized longitudinal tau variability in human Alzheimer's disease, identifying four trajectories of tau deposition with distinct clinical features. The results suggest that variation in tau pathology is common and systematic, potentially necessitating a re-examination of the notion of 'typical AD' and a revisiting of tau pathological staging.

NATURE MEDICINE (2021)

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Yang Zhou et al.

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ACS CHEMICAL NEUROSCIENCE (2021)

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Cryptic Sites in Tau Fibrils Explain the Preferential Binding of the AV-1451 PET Tracer toward Alzheimer's Tauopathy

N. Arul Murugan et al.

Summary: Research shows that different tau tracers have different binding sites for tau fibrils associated with different tauopathies, offering the potential for developing tracers with high selectivity for specific tauopathies. By using various computational methods and experimental techniques, it is possible to better understand the binding properties of tau tracers in different tauopathies.

ACS CHEMICAL NEUROSCIENCE (2021)

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Three-dimensional mapping of neurofibrillary tangle burden in the human medial temporal lobe

Paul A. Yushkevich et al.

Summary: This study utilized ex vivo MRI and dense serial histological imaging to construct three-dimensional quantitative maps of neurofibrillary tangle burden in the medial temporal lobe, revealing significant variation along different anatomical regions. The findings provide valuable insights into the distribution of this neurodegenerative pathology and may support the development and validation of neuroimaging biomarkers.

BRAIN (2021)

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Binding characteristics of [18F]PI-2620 distinguish the clinically predicted tau isoform in different tauopathies by PET

Mengmeng Song et al.

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Heiko Kroth et al.

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LANCET NEUROLOGY (2021)

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NATURE MEDICINE (2021)

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Harald Hampel et al.

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Amyloid tracers binding sites in autosomal dominant and sporadic Alzheimer's disease

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Distinct binding of PET ligands PBB3 and AV-1451 to tau fibril strains in neurodegenerative tauopathies

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18F-THK5351: A Novel PET Radiotracer for Imaging Neurofibrillary Pathology in Alzheimer Disease

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Diverging longitudinal changes in astrocytosis and amyloid PET in autosomal dominant Alzheimer's disease

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Preclinical Characterization of 18F-MK-6240, a Promising PET Tracer for In Vivo Quantification of Human Neurofibrillary Tangles

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PET Imaging of Tau Deposition in the Aging Human Brain

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[18F]Flutemetamol amyloid-beta PET imaging compared with [11C]PIB across the spectrum of Alzheimer's disease

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Amyloid-β and Tau The Trigger and Bullet in Alzheimer Disease Pathogenesis

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[18F]T807, a novel tau positron emission tomography imaging agent for Alzheimer's disease

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Amyloid tracers detect multiple binding sites in Alzheimer's disease brain tissue

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Early Clinical PET Imaging Results with the Novel PHF-Tau Radioligand [F-18]-T807

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Positron emission tomography radioligands for in vivo imaging of Aβ plaques

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Head-to-Head Comparison of 11C-PiB and 18F-AZD4694 (NAV4694) for β-Amyloid Imaging in Aging and Dementia

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Novel 18F-Labeled Arylquinoline Derivatives for Noninvasive Imaging of Tau Pathology in Alzheimer Disease

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Imaging of Tau Pathology in a Tauopathy Mouse Model and in Alzheimer Patients Compared to Normal Controls

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Regional variability of imaging biomarkers in autosomal dominant Alzheimer's disease

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Clinical Validation of 18F-AZD4694, an Amyloid-β-Specific PET Radioligand

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Low PiB PET retention in presence of pathologic CSF biomarkers in Arctic APP mutation carriers

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PIB binding in aged primate brain: Enrichment of high-affinity sites in humans with Alzheimer's disease

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Preclinical Properties of 18F-AV-45: A PET Agent for Aβ Plaques in the Brain

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In vitro characterization of Pittsburgh compound-B binding to Lewy bodies

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Imaging of amyloid burden and distribution in cerebral amyloid angiopathy

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2-(2-[2-dimethylaminothiazol-5-yl]ethenyl)-6-(2-[fluoro]ethoxy)benzoxazole: A novel PET agent for in vivo detection of dense amyloid plaques in Alzheimer's disease patients

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Phases of Aβ-deposition in the human brain and its relevance for the development of AD

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Binding characteristics of radiofluorinated 6-dialkylamino-2-naphthylethylidene derivatives as positron emission tomography imaging probes for β-amyloid plaques in Alzheimer's disease

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