<sup>18</sup>F-AV-1451 tau PET imaging correlates strongly with tau neuropathology in<i>MAPT</i>mutation carriers

Smith, Ruben; Puschmann, Andreas; Schöll, Michael; Ohlsson, Tomas; Swieten, John van; Honer, Michael; Englund, Elisabet; Hansson, Oskar

doi:10.1093/brain/aww163

Cited by 158 publications

(170 citation statements)

References 27 publications

Supporting

Mentioning

158

Contrasting

Order By: Relevance

“…Additionally, 18 F-AV-1451 retention is related to MRI and DTI at baseline and appears to increase over disease course in brain regions containing with 4Rtau pathological burden. These findings converge with other post-mortem evidence of 18 F-AV-1451 retention in MAPT mutation carriers [9] and a patient with CBD[3]. However, single case data should be interpreted cautiously and future cohort studies, additional autoradiography studies, and direct comparisons between CBD and AD are necessary to validate 18 F-AV-1451 imaging for 4Rtau in CBD.…”

supporting

confidence: 83%

Multimodal evaluation demonstrates in vivo 18F-AV-1451 uptake in autopsy-confirmed corticobasal degeneration

et al. 2016

View full text Add to dashboard Cite

supporting

confidence: 83%

Multimodal evaluation demonstrates in vivo 18F-AV-1451 uptake in autopsy-confirmed corticobasal degeneration

et al. 2016

View full text Add to dashboard Cite

“…[67][68][69][70][71] The favourable pharmacokinetics of those tracers [72][73][74] completed the requirements for Phase I. A number of rather small and non-consecutive Phase II studies have already reported good discrimination between healthy volunteers and AD patients, 67,[75][76][77][78] with preliminary evidence, available for only one of the tracers (AV-1451), supporting the agreement between antemortem PET quantification of the tracer retention and postmortem evidence of tau pathology in the same non-AD patients, a carrier of a MAPT mutation (p.R406W), and two patients with corticobasal degeneration, although questions remain about the specific target of the tracer 58,79,80 (Phase II, SA 2). Further research on tau PET imaging is required to understand the binding characteristics of the different tracers, before exploring further the clinical validity of this novel biomarker.…”

Section: Sa3mentioning

confidence: 81%

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

Frisoni

Boccardi

Barkhof

et al. 2017

The Lancet Neurology

Self Cite

512

480

View full text Add to dashboard Cite

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...

show abstract

“…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%

“…These findings suggest the high affinity of [ 18 F]AV1451 for PHF tau inclusions containing all 6 tau isoforms, as found in AD and in a subset of MAPT mutations, including V337M. 14,19 It is unlikely that […”

Section: Controlsmentioning

confidence: 96%

Frontotemporal dementia with the V337M MAPT mutation

et al. 2017

View full text Add to dashboard Cite

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.

show abstract

¹⁸F-AV-1451 tau PET imaging correlates strongly with tau neuropathology inMAPTmutation carriers

Cited by 158 publications

References 27 publications

Multimodal evaluation demonstrates in vivo 18F-AV-1451 uptake in autopsy-confirmed corticobasal degeneration

Multimodal evaluation demonstrates in vivo 18F-AV-1451 uptake in autopsy-confirmed corticobasal degeneration

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

Frontotemporal dementia with the V337M MAPT mutation

Contact Info

Product

Resources

About

18F-AV-1451 tau PET imaging correlates strongly with tau neuropathology inMAPTmutation carriers

Cited by 158 publications

References 27 publications

Multimodal evaluation demonstrates in vivo 18F-AV-1451 uptake in autopsy-confirmed corticobasal degeneration

Multimodal evaluation demonstrates in vivo 18F-AV-1451 uptake in autopsy-confirmed corticobasal degeneration

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

Frontotemporal dementia with the V337M MAPT mutation

Contact Info

Product

Resources

About

¹⁸F-AV-1451 tau PET imaging correlates strongly with tau neuropathology inMAPTmutation carriers