[18F]AV-1451 tau-PET uptake does correlate with quantitatively measured 4R-tau burden in autopsy-confirmed corticobasal degeneration

Josephs, Keith A.; Whitwell, Jennifer L.; Tacik, Paweł; Duffy, Joseph R.; Senjem, Matthew L.; Tosakulwong, Nirubol; Jack, Clifford R.; Lowe, Val J.; Dickson, Dennis W.; Murray, Melissa E.

doi:10.1007/s00401-016-1618-1

Cited by 119 publications

(122 citation statements)

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“…12,[16][17][18] [ 18 F]THK5317 retention increased in both these patients over time, predominantly in the basal ganglia and frontotemporal areas, and [ 18 F]FDG uptake decreased isocortically. Nonetheless, there were differences between the two cases that might indicate that they were at different stages in the progression of the pathology.…”

Section: Discussionmentioning

confidence: 88%

“…Case series have revealed high regional retention of the tau tracers in patients with clinical diagnoses of corticobasal syndrome (CBS), but the regional distribution in these cases was different from that in patients with AD. 12,[16][17][18] The understanding of the in vivo propagation of the pathology in the different degenerative tauopathies, however, remains elusive.…”

Section: Introductionmentioning

confidence: 99%

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Longitudinal changes of tau PET imaging in relation to hypometabolism in prodromal and Alzheimer’s disease dementia

et al. 2017

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The development of tau-specific positron emission tomography (PET) tracers allows imaging in vivo the regional load of tau pathology in Alzheimer's disease (AD) and other tauopathies. Eighteen patients with baseline investigations enroled in a 17-month follow-up study, including 16 with AD (10 had mild cognitive impairment and a positive amyloid PET scan, that is, prodromal AD, and six had AD dementia) and two with corticobasal syndrome. INTRODUCTIONThe aggregation of abnormally hyperphosphorylated tau protein into paired helical filaments is a key aspect of the pathology of Alzheimer's disease (AD). 1 Both the regional distribution of tau pathology in the brains of patients with AD and the sequential staging of its progression have been extensively described in postmortem studies. 2-5 These studies indicated, for the first time, that an early and relatively long preclinical phase of tau aggregation precedes the symptomatic stages of AD. 6,7 Despite this, the time course of tau pathology propagation, especially in relation to changes in the concomitant clinical and cognitive profiles of the individual patients, remains largely speculative because of the inherent limitations of post-mortem studies.During the past 5 years, the development of tau-specific positron emission tomography (PET) tracers 8 has provided a valuable addition to the neuroimaging arsenal. THK5317 [(S)-THK5117], a well characterised tau-specific tracer, 9-11 showed high retention in patients with AD with a regional pattern matching that of the distribution of tau pathology described by post-mortem studies. 12 Cross-sectionally, high load of tau pathology, as measured with THK5317 PET, was associated with

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Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Longitudinal changes of tau PET imaging in relation to hypometabolism in prodromal and Alzheimer’s disease dementia

et al. 2017

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“…14,[18][19][20] We describe clinical, structural MRI, and [ A 30-year-old right-handed man developed compulsions, irritability, and mental inflexibility. Later, he developed difficulties with memory, completion of tasks, and orientation.…”

Section: Discussionmentioning

confidence: 99%

Frontotemporal dementia with the V337M MAPT mutation

et al. 2017

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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 microtubuleassociated 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. We describe clinical, structural MRI, and [18 F]AV1451 PET findings in a V337M MAPT mutation carrier affected by FTD and pathologic findings in his affected mother and in an unrelated V337M MAPT carrier also affected with FTD. The biochemical similarity between paired helical filament tau in AD and MAPT V337M predicts that the tau pathology associated with this mutation constitutes a compelling target for [18 F]AV1451 imaging.Results: We found a strong association between topography and degree of [18 F]AV1451 tracer retention in the proband and distribution of tau pathology in the brain of the proband's mother and the unrelated V337M mutation carrier. We also found a significant correlation between the degree of regional MRI brain atrophy and the extent of Frontotemporal dementia (FTD) is the second most prevalent type of dementia before age 65.

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“…Tau PET was not included as it is an emerging technology currently used only in research (phase I/phase II development stages), as briefly outlined further on. 58 The roadmap we propose provides a general framework that can benefit other technologies or techniques, including tau PET.…”

Section: Research Priorities For Ad Biomarker Validation To Launch Phmentioning

confidence: 99%

Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers

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Boccardi

Barkhof

et al. 2017

The Lancet Neurology

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Biomarkers sensitive to functional impairment, neuronal loss, tau, and amyloid pathology based on MR, PET, and CSF studies are increasingly used to diagnose Alzheimer's disease (AD), but clinical validation is incomplete, hampering reimbursement by payers, widespread clinical implementation, and impacting on health care quality. An expert group convened to develop a strategic research agenda to foster the clinical validation of AD biomarkers. These demonstrated sufficient evidence of analytical validity (phase I of a structured framework adapted from oncology). Research priorities were identified based on incomplete clinical validity (phases II and III), and clinical utility (phases IV and V). Priorities included: definition of the assays; reading procedures and thresholds for normality; performance in detecting early disease; accounting for the effect of covariates; diagnostic algorithms comprising combinations of biomarkers; and developing best practice guidelines for the use of biomarkers in qualified memory clinics in the context of phase IV studies. 5 GlossaryBiomarker. An objective measure of a biological or pathogenic process with the purpose of evaluating disease risk or prognosis, guiding clinical diagnosis or monitoring therapeutic interventions. While the term originally referred to traceable substances produced by or introduced into an organism, it later evolved to any measurable parameter, including those obtained via imaging procedures.Roadmap. Objective-oriented, structured, and efficient action plan. In science and technology also called "strategic research agenda".Alzheimer's disease (AD) dementia. Traditionally and according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria, Alzheimer's disease was defined as a syndrome with progressive cognitive impairment severe enough to impact on daily activities. A diagnosis of Alzheimer's disease could only be made after exclusion of other possible causes. 1 Sixty-five to 80% of cases of patients fulfilling these criteria have Alzheimer's pathology (plaques and tangles), the remainder having a range of other pathologies. In order to increase diagnostic certainty, contemporary criteria for AD dementia incorporate biomarker evidence for different aspects of Alzheimer's pathology, including imaging (magnetic resonance imaging -MRI -measures of atrophy; 18 F-fluorodeoxyglucose-positron emission tomography -FDG-PET -measures of cerebral hypometabolism; amyloid PET measures of fibrillar β-amyloid -A -deposition) and cerebrospinal fluid -CSF (decreased levels of A42, increased levels of tau and phospho-tau). 2,3 Alzheimer's disease process. Recognizing that AD pathology is present many years before symptoms emerge, new criteria classify the disease process on a continuum from asymptomatic to prodromal and finally to dementia stage. 4 Individuals at the asymptomatic stage can only be identified by biomarkers of Alzheimer's pathology. None...

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[18F]AV-1451 tau-PET uptake does correlate with quantitatively measured 4R-tau burden in autopsy-confirmed corticobasal degeneration

Cited by 119 publications

References 10 publications

Longitudinal changes of tau PET imaging in relation to hypometabolism in prodromal and Alzheimer’s disease dementia

Longitudinal changes of tau PET imaging in relation to hypometabolism in prodromal and Alzheimer’s disease dementia

Frontotemporal dementia with the V337M MAPT mutation

Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers

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