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Q351R MAPT mutation is associated with a mixed 3R/4R tauopathy and a slowly progressive cognitive, behavioural and parkinsonian syndrome
  1. Erin Halley Squillacote Drazich-Taylor1,
  2. Emily Todd1,
  3. Rhian Convery1,
  4. Martina Bocchetta1,
  5. Mica Clarke1,
  6. Jason D Warren1,
  7. Nick C Fox1,
  8. Tamas Revesz2,
  9. Jonathan Daniel Rohrer1
  1. 1Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK
  2. 2UCL Queen Square Institute of Neurology, Queen Square Brain Bank for Neurological Disorders, London, UK
  1. Correspondence to Dr Jonathan Daniel Rohrer, Department of Neurodegenerative Disease, University College London, London, WC1N 3BG, UK; j.rohrer{at}ucl.ac.uk

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Introduction

We have previously reported the initial clinical and imaging findings of a woman with a novel MAPT Q351R mutation.1 2 We continued to assess her following these case reports until she died and have now analysed her brain at postmortem. Her case was of unique interest due to the novelty of the mutation and its clinical features1 as well as the strong binding seen on flortaucipir positron emission tomography (PET) imaging,2 which was suggestive of a very specific pathological finding, that of a mixed 3R/4R tauopathy, similar to that seen in other MAPT mutations (V337M and R406W),3 4 and consistent with the same type of paired helical filament tau pathology seen in Alzheimer’s disease (AD). She is the first patient with this mutation to come to autopsy and we report the findings in this study.

Methods

A patient with a Q351R mutation was seen over a 20-year period, during which time she was assessed clinically, and with repeated MR brain imaging (11 scans in total) as well as flortaucipir PET imaging. In this report, her MR imaging is compared against a cohort of 43 healthy individuals (all women; mean age 61.5 years old, range 49.7–68.5 years old). All participants gave their consent to take part. At the time of death, her brain was donated to the Queen Square Brain Bank for Neurological Disorders and underwent postmortem analysis.

Results

Clinical history

She presented to a specialist cognitive neurology clinic in her late 40s with a 4-year history of amnestic symptoms and mild behavioural change, mainly in the form of apathy. Neurological examination was normal, but her initial …

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Footnotes

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  • Contributors JDR and EHSD-T designed the study, analysed the data and wrote the manuscript. TR analysed the pathological data and reviewed the manuscript. ET, RC, MB, MC, JDW and NCF helped with data collection, analysis and review of the manuscript.

  • Funding The Dementia Research Centre is supported by Alzheimer's Research UK, Alzheimer's Society, Brain Research UK, and The Wolfson Foundation. This work was supported by the NIHR UCL/H Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility, and the UK Dementia Research Institute, which receives its funding from UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK. JDR is supported by the Miriam Marks Brain Research UK Senior Fellowship and has received funding from an MRC Clinician Scientist Fellowship (MR/M008525/1) and the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). JDW is supported by the Alzheimer’s Society and by the NIHR UCLH Biomedical Research Centre. NCF is supported by the NIHR UCL/H Biomedical Research Centre and the UK Dementia Research Institute, which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.