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  3. Tau accumulation in autosomal dominant Alzheimer's disease: a longitudinal [18F]flortaucipir study

Tau accumulation in autosomal dominant Alzheimer's disease: a longitudinal [18F]flortaucipir study

  • Alzheimers Res Ther. 2023 May 25;15(1):99. doi: 10.1186/s13195-023-01234-5.
Antoinette O'Connor # 1 2,  David M Cash # 3,  Teresa Poole 3 4,  Pawel J Markiewicz 5,  Maggie R Fraser 3,  Ian B Malone 3,  Jieqing Jiao 5,  Philip S J Weston 3,  Shaney Flores 6,  Russ Hornbeck 6,  Eric McDade 7,  Michael Schöll 3 8,  Brian A Gordon 6,  Randall J Bateman 7,  Tammie L S Benzinger 6,  Nick C Fox 3 9
Affiliations

Affiliations

  • 1 Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK. Antoinette.o'connor@ucl.ac.uk.
  • 2 UK Dementia Research Institute at UCL, London, UK. Antoinette.o'connor@ucl.ac.uk.
  • 3 Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK.
  • 4 Department of Medical Statistics, London School of Hygiene & Tropical Medicine, London, UK.
  • 5 Centre for Medical Image Computing, Medical Physics and Biomedical Engineering, UCL, London, UK.
  • 6 Department of Radiology, Washington University in St. Louis, St. Louis, MO, USA.
  • 7 Department of Neurology, Washington University in St. Louis, St. Louis, MO, USA.
  • 8 Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
  • 9 UK Dementia Research Institute at UCL, London, UK.
  • # Contributed equally.
PMID: 37231491 DOI: 10.1186/s13195-023-01234-5
Abstract

Cortical tau accumulation is a key pathological event that partly defines Alzheimer's disease (AD) onset and is associated with cognitive decline and future disease progression. However, an improved understanding of the timing and pattern of early tau deposition in AD and how this may be tracked in vivo is needed. Data from 59 participants involved in two longitudinal cohort studies of autosomal dominant AD (ADAD) were used to investigate whether tau PET can detect and track presymptomatic change; seven participants were symptomatic, and 52 were asymptomatic but at a 50% risk of carrying a pathogenic mutation. All had baseline flortaucipir (FTP) PET, MRI and clinical assessments; 26 individuals had more than one FTP PET scan. Standardised uptake value ratios (SUVRs) in prespecified regions of interest (ROIs) were obtained using inferior cerebellar grey matter as the reference region. We compared the changes in FTP SUVRs between presymptomatic carriers, symptomatic carriers and non-carriers, adjusting for age, sex and study site. We also investigated the relationship between regional FTP SUVRs and estimated years to/from symptom onset (EYO). Compared to both non-carriers and presymptomatic carriers, FTP SUVRs were significantly higher in symptomatic carriers in all ROIs tested (p < 0.001). There were no significant regional differences between presymptomatic carriers and non-carriers in FTP SUVRs, or their rates of change (p > 0.05), although increased FTP signal uptake was seen posteriorly in some individuals around the time of expected symptom onset. When we examined the relationship of FTP SUVR with respect to EYO, the earliest significant regional difference between mutation carriers and non-carriers was detected within the precuneus prior to estimated symptom onset in some cases. This study supports preliminary studies suggesting that presymptomatic tau tracer uptake is rare in ADAD. In cases where early uptake was seen, there was often a predilection for posterior regions (the precuneus and post-cingulate) as opposed to the medial temporal lobe, highlighting the importance of examining in vivo tau uptake beyond the confines of traditional Braak staging.

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