18F-AV-1451 tau PET imaging correlates strongly with tau neuropathology in MAPT mutation carriers

Research output: Contribution to journalArticle

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 18F-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 18F-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 18F-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 (18F-flutemetamol) positron emission tomography scans were negative in all cases, as were stainings of brain sections for amyloid. This provides strong evidence that 18F-AV-1451 positron emission tomography can be used to accurately quantify in vivo the regional distribution of hyperphosphorylated tau protein.

Details

Authors
Organisations
External organisations
  • Skåne University Hospital
  • University of Gothenburg
  • Erasmus University Medical Center
  • Roche Innovation Center
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology

Keywords

  • Alzheimer's disease, frontotemporal dementia, MAPT R406W mutation, positron emission tomography, tau
Original languageEnglish
Pages (from-to)2372-2379
Number of pages8
JournalBrain
Volume139
Issue number9
Publication statusPublished - 2016 Sep 1
Publication categoryResearch
Peer-reviewedYes