Tau positron emission tomography imaging in C9orf72 repeat expansion carriers

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.

Conflict of interest statement

CONFLICT OF INTEREST

© 2019 EAN.

Figures

Figure 1.

Tau PET uptake in C9orf72 expansion carriers and controls. A) Representative coronal, sagittal, and axial images showing regional distribution of cerebellar gray-normalized AV-1451 SUVR values and paired T2-weighted MRI images in C9orf72 expansion (right) and control participants (left). Entorhinal cortex is outlined in red. B) AV-1451 SUVR values in twelve brain regions. Statistics by student’s t-test using a Bonferroni significance level of 0.0042. C) Post-mortem analysis of hippocampus from a C9orf72 participant with tau PET SUVR of 1.26. Sections stained with AT8 antibody show tau reactivity (scale bar: 50 μm) in the entorhinal cortex. Inset shows tau pathology at higher magnification (scale bar: 20 μm). Entorhinal cortical sections stained for β-amyloid (BA) did not display reactivity (scale bar: 50 μm).