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In vivo changes in microglial activation and amyloid deposits in brain regions with hypometabolism in Alzheimer’s disease

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Amyloid β protein (Aβ) is known as a pathological substance in Alzheimer’s disease (AD) and is assumed to coexist with a degree of activated microglia in the brain. However, it remains unclear whether these two events occur in parallel with characteristic hypometabolism in AD in vivo. The purpose of the present study was to clarify the in vivo relationship between Aβ accumulation and neuroinflammation in those specific brain regions in early AD.

Methods

Eleven nootropic drug-naïve AD patients underwent a series of positron emission tomography (PET) measurements with [11C](R)PK11195, [11C]PIB and [18F]FDG and a battery of cognitive tests within the same day. The binding potentials (BPs) of [11C](R)PK11195 were directly compared with those of [11C]PIB in the brain regions with reduced glucose metabolism.

Results

BPs of [11C](R)PK11195 and [11C]PIB were significantly higher in the parietotemporal regions of AD patients than in ten healthy controls. In AD patients, there was a negative correlation between dementia score and [11C](R)PK11195 BPs, but not [11C]PIB, in the limbic, precuneus and prefrontal regions. Direct comparisons showed a significant negative correlation between [11C](R)PK11195 and [11C]PIB BPs in the posterior cingulate cortex (PCC) (p < 0.05, corrected) that manifested the most severe reduction in [18F]FDG uptake.

Conclusion

A lack of coupling between microglial activation and amyloid deposits may indicate that Aβ accumulation shown by [11C]PIB is not always the primary cause of microglial activation, but rather the negative correlation present in the PCC suggests that microglia can show higher activation during the production of Aβ in early AD.

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Acknowledgments

We would like to thank Dr. Mitsuo Kaneko (Kaneko Clinic), Dr. Masanobu Sakamoto and Messrs. Toshihiko Kanno and Yasuo Tanizaki (Hamamatsu Medical Center), Yutaka Naito (Japan Environment Research Corporation), Masami Futatsubashi, Akihito Oda and Ms. Tomomi Shinke (Hamamatsu Photonics KK) for their support. This work was supported by Research Grants from the Japanese Ministry of Health, Labor and Welfare, and Ministry of Economy, Trade and Industry, and NEDO and the Takeda Science Foundation.

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Masamichi Yokokura, Norio Mori, Yujiro Yoshihara, Tomoyasu Wakuda, Kiyokazu Takebayashi, Yasuhide Iwata & Kazuhiko Nakamura

  2. Laboratory of Human Imaging Research, Molecular Imaging Frontier Research Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan

    Shunsuke Yagi & Yasuomi Ouchi

  3. Central Research Laboratory, Hamamatsu Photonics K.K., Hamamatsu, Japan

    Etsuji Yoshikawa

  4. Department of Psychiatry and Neurobiology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan

    Mitsuru Kikuchi

  5. Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Genichi Sugihara, Shiro Suda, Kenji J. Tsuchiya & Katsuaki Suzuki

  6. Department of Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Takatoshi Ueki

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  1. Masamichi Yokokura
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Correspondence to Yasuomi Ouchi.

Electronic Supplementary Material

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Supplementary Table 1

Results of SPM analysis (DOC 61 kb)

Supplementary Table 2

Pearson correlation analyses in the AD group (DOC 65 kb)

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Yokokura, M., Mori, N., Yagi, S. et al. In vivo changes in microglial activation and amyloid deposits in brain regions with hypometabolism in Alzheimer’s disease. Eur J Nucl Med Mol Imaging 38, 343–351 (2011). https://doi.org/10.1007/s00259-010-1612-0

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  • DOI: https://doi.org/10.1007/s00259-010-1612-0

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