title: 18F-AV-1451 tau PET imaging correlates strongly with tau neuropathology in MAPT mutation carriers.
abstract: Tau positron emission tomography ligands provide the novel possibility to image tau pathology in vivo However, little is known about how in vivo brain uptake of tau positron emission tomography ligands relates to tau aggregates observed post-mortem. We performed tau positron emission tomography imaging with (18)F-AV-1451 in three patients harbouring a p.R406W mutation in the MAPT gene, encoding tau. This mutation results in 3- and 4-repeat tau aggregates similar to those in Alzheimer's disease, and many of the mutation carriers initially suffer from memory impairment and temporal lobe atrophy. Two patients with short disease duration and isolated memory impairment exhibited (18)F-AV-1451 uptake mainly in the hippocampus and adjacent temporal lobe regions, correlating with glucose hypometabolism in corresponding regions. One patient died after 26 years of disease duration with dementia and behavioural deficits. Pre-mortem, there was (18)F-AV-1451 uptake in the temporal and frontal lobes, as well as in the basal ganglia, which strongly correlated with the regional extent and amount of tau pathology in post-mortem brain sections. Amyloid-β ((18)F-flutemetamol) positron emission tomography scans were negative in all cases, as were stainings of brain sections for amyloid. This provides strong evidence that (18)F-AV-1451 positron emission tomography can be used to accurately quantify in vivo the regional distribution of hyperphosphorylated tau protein.
authors.affiliation: 1 Department of Clinical Sciences Lund, Department of Neurology, Lund University, Sweden 2 Department of Neurology and Rehabilitation Medicine, Skåne University Hospital, Lund, Sweden Ruben.Smith@med.lu.se oskar.hansson@med.lu.se.
authors.forename: Ruben
authors.initials: R
authors.lastname: Smith
authors.affiliation: 1 Department of Clinical Sciences Lund, Department of Neurology, Lund University, Sweden 2 Department of Neurology and Rehabilitation Medicine, Skåne University Hospital, Lund, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Puschmann
authors.affiliation: 3 Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Sweden 4 MedTech West and the Division of Clinical Neuroscience, Gothenburg University, Gothenburg, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Schöll
authors.affiliation: 5 Department of Radiation physics, Skåne University Hospital, Lund, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Ohlsson
authors.affiliation: 6 Department of Neurology, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: John
authors.initials: J
authors.lastname: van Swieten
authors.affiliation: 7 Roche Pharmaceutical Research and Early Development, Neuroscience Discovery and Biomarkers, Roche Innovation Center, Basel, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Honer
authors.affiliation: 8 Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Sweden.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Englund
authors.affiliation: 3 Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Sweden 9 Memory Clinic, Skåne University Hospital, Malmö, Sweden Ruben.Smith@med.lu.se oskar.hansson@med.lu.se.
authors.forename: Oskar
authors.initials: O
authors.lastname: Hansson
mesh_terms: D000368:Aged; D001284:Atrophy / Q000473:pathology; D002243:Carbolines; D003704:Dementia / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D005260:Female; D006579:Heterozygote; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D049268:Positron-Emission Tomography / Q000379:methods*; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002243:Carbolines; C054369:MAPT protein, human; D016875:tau Proteins; C000591008:7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole
keywords: Alzheimer’s disease; MAPT R406W mutation; frontotemporal dementia; positron emission tomography; tau