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In vivo imaging of synaptic loss in Alzheimer’s disease with [18F]UCB-H positron emission tomography

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Abstract

Purpose

Loss of brain synapses is an early pathological feature of Alzheimer’s disease. The current study assessed synaptic loss in vivo with positron emission tomography and an 18F-labelled radiotracer of the synaptic vesicle protein 2A, [18F]UCB-H.

Methods

Twenty-four patients with mild cognitive impairment or Alzheimer’s disease and positive [18F]Flutemetamol amyloid-PET were compared to 19 healthy controls. [18F]UCB-H brain uptake was quantified with Logan graphical analysis using an image-derived blood input function. SPM12 and regions-of-interest (ROI) analyses were used for group comparisons of regional brain distribution volumes and for correlation with cognitive measures.

Results

A significant decrease of [18F]UCB-H uptake was observed in several cortical areas (11 to 18% difference) and in the thalamus (16% difference), with the largest effect size in the hippocampus (31% difference). Reduced hippocampal uptake was related to patients’ cognitive decline (ROI analysis) and unawareness of memory problems (SPM and ROI analyses).

Conclusions

The findings thus highlight predominant synaptic loss in the hippocampus, confirming previous autopsy-based studies and a recent PET study with an 11C-labelled SV2A radiotracer. [18F]UCB-H PET allows to image in vivo synaptic changes in Alzheimer’s disease and to relate them to patients’ cognitive impairment.

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Notes

  1. Signal from the two carotids was used to increase the quality of the data, but distribution volumes obtained by considering the signal from the left and right carotid independently were highly similar (left/right ratio = 0.99 ± 0.05) and each was also highly similar to the distribution volume considering the two carotids together (left/total ratio, 0.99 ± 0.01; right/total ratio, 0.99 ± 0.04).

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Funding

This work was supported by grants from Belgian Interuniversity Attraction Pole (IUAP 7/11), ULiege Research Concerted Action (ARC 12/17-01), Special Research Funds classical grant 2016 (Faculty of Medicine, University of Liege, Belgium), FRS-FNRS. Patient selection was supported by an Investigator Sponsored Study (ISS290) from GE Healthcare for [18F]flutemetamol delivery, and the Walloon Region Public Private Partnership NeuroCom, with the ULiege and UCB Pharma as partners. A. Plenevaux is a research director and C. Bastin is a research associate at the FRS-FNRS Belgium. We thank Nicolas Antoine for providing [18F]flutemetamol data, Lola Danet for help with localization of thalamic nuclei in Morel’s atlas and Roland Hustinx and Claire Bernard (Liege University Hospital) for providing [18F]FDG-PET images.

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Author notes

  1. Christine Bastin and Mohamed Ali Bahri contributed equally to this work.

Authors and Affiliations

  1. GIGA-Cyclotron Research Center-in vivo imaging, University of Liège, Allée du 6 Août, B30, 4000, Liege, Belgium

    Christine Bastin, Mohamed Ali Bahri, François Meyer, Marine Manard, Emma Delhaye, Alain Plenevaux, Guillaume Becker, Alain Seret, Christine Mella, Fabrice Giacomelli, Christian Degueldre, Evelyne Balteau, André Luxen & Eric Salmon

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  1. Christine Bastin
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Correspondence to Christine Bastin.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee (Ethics Committee of the Liege University Hospital, reference number EudraCT 2014–000286-50) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Bastin, C., Bahri, M.A., Meyer, F. et al. In vivo imaging of synaptic loss in Alzheimer’s disease with [18F]UCB-H positron emission tomography. Eur J Nucl Med Mol Imaging 47, 390–402 (2020). https://doi.org/10.1007/s00259-019-04461-x

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