Tau positron emission tomography imaging in C9orf72 repeat expansion carriers

Eur J Neurol. 2019 Sep;26(9):1235-1239. doi: 10.1111/ene.13940. Epub 2019 Mar 25.

Abstract

Background and purpose: AV-1451 (18 F-AV-1451, flortaucipir) positron emission tomography was performed in C9orf72 expansion carriers to assess tau accumulation and disease manifestation.

Methods: Nine clinically characterized C9orf72 expansion carriers and 18 age- and gender- matched cognitively normal individuals were psychometrically evaluated and underwent tau positron emission tomography imaging. The regional AV-1451 standard uptake value ratios from multiple brain regions were analyzed. Spearman correlation was performed to relate the AV-1451 standard uptake value ratio to clinical, psychometric and cerebrospinal fluid measures.

Results: C9orf72 expansion carriers had increased AV-1451 binding in the entorhinal cortex compared to controls. Primary age-related tauopathy was observed postmortem in one patient. AV-1451 uptake did not correlate with clinical severity, disease duration, psychometric performance or cerebrospinal fluid markers.

Conclusion: C9orf72 expansion carriers exhibited increased AV-1451 uptake in entorhinal cortex compared to cognitively normal controls, suggesting a propensity for primary age-related tauopathy. However, AV-1451 accumulation was not associated with psychometric performance in our cohort.

Keywords: AV-1451; C9orf72; amyotrophic lateral sclerosis; positron emission tomography; tau.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • C9orf72 Protein / genetics*
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / metabolism*
  • Cohort Studies
  • DNA Repeat Expansion
  • Entorhinal Cortex / diagnostic imaging
  • Entorhinal Cortex / metabolism*
  • Female
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Positron-Emission Tomography*
  • Tauopathies / complications
  • Tauopathies / diagnostic imaging
  • Tauopathies / metabolism*
  • tau Proteins / metabolism*

Substances

  • C9orf72 Protein
  • C9orf72 protein, human
  • tau Proteins

Associated data

  • GENBANK/NCT02414230
  • GENBANK/NS048056