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Low density of sigma1 receptors in early Alzheimer’s disease

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Abstract

Objective

The sigma1 receptor is considered to be involved in cognitive function. A postmortem study reported that the sigma1 receptors were reduced in the hippocampus in Alzheimer’s disease (AD). However, in vivo imaging of sigma1 receptors in the brain of AD patients has not been reported. The aim of this study is to investigate the mapping of sigma1 receptors in AD using [11C]SA4503 positron emission tomography (PET).

Methods

We studied five AD patients and seven elderly volunteers. A dynamic series of decay-corrected PET data acquisition was performed for 90 min starting at the time of the injection of 500 MBq of [11C]SA4503. A two-tissue three-compartment model was used to estimate K 1, k 2, k 3, k 4, and the delay between metabolite-corrected plasma and tissue time activity using a Gauss-Newton algorithm. The ratio of k 3 to k 4 was computed as the binding potential (BP), which is linearly related to the density of sigma1 receptors. Unpaired t tests were used to compare K 1 and BP in patients with AD and normal subjects.

Results

As compared with normals, BP in the AD was significantly lower in the frontal, temporal, and occipital lobe, cerebellum and thalamus, whereas K 1 was significantly lower in the parietal lobe.

Conclusions

[11C]SA4503 PET can demonstrate that the density of cerebral and cerebellar sigma1 receptors is reduced in early AD.

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Authors and Affiliations

  1. Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan

    Masahiro Mishina, Masashi Ohyama, Kenji Ishii, Yuichi Kimura, Kei-ichi Oda, Kazunori Kawamura, Toru Sasaki & Kiichi Ishiwata

  2. Department of Neurology, Nephrology and Rheumatology, Nippon Medical School, Tokyo, Japan

    Masahiro Mishina, Masashi Ohyama, Shin Kitamura & Yasuo Katayama

  3. Neurological Institute, Nippon Medical School Chiba-Hokusoh Hospital, 1715 Kamagari, Imba-mura, Imba-gun, Chiba, 270-1694, Japan

    Masahiro Mishina & Shiro Kobayashi

  4. Department of Internal Medicine, Nippon Medical School Musashi Kosugi Hospital, Kanagawa, Japan

    Shin Kitamura

  5. Biophysics Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan

    Yuichi Kimura

  6. Center for Integrated Brain Science, Brain Research Institute, University of Niigata, Niigata, Japan

    Kazunori Kawamura

  7. Research Team for Molecular Biomarkers, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan

    Toru Sasaki

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  1. Masahiro Mishina
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  2. Masashi Ohyama
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Correspondence to Masahiro Mishina.

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Mishina, M., Ohyama, M., Ishii, K. et al. Low density of sigma1 receptors in early Alzheimer’s disease. Ann Nucl Med 22, 151–156 (2008). https://doi.org/10.1007/s12149-007-0094-z

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  • DOI: https://doi.org/10.1007/s12149-007-0094-z

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