European Journal of Nuclear Medicine and Molecular Imaging

, Volume 38, Issue 2, pp 343–351

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

  • Masamichi Yokokura
  • Norio Mori
  • Shunsuke Yagi
  • Etsuji Yoshikawa
  • Mitsuru Kikuchi
  • Yujiro Yoshihara
  • Tomoyasu Wakuda
  • Genichi Sugihara
  • Kiyokazu Takebayashi
  • Shiro Suda
  • Yasuhide Iwata
  • Takatoshi Ueki
  • Kenji J. Tsuchiya
  • Katsuaki Suzuki
  • Kazuhiko Nakamura
  • Yasuomi Ouchi
Original Article

DOI: 10.1007/s00259-010-1612-0

Cite this article as:
Yokokura, M., Mori, N., Yagi, S. et al. Eur J Nucl Med Mol Imaging (2011) 38: 343. doi:10.1007/s00259-010-1612-0

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.

Keywords

Alzheimer’s diseaseMicrogliaAmyloid β proteinPositron emission tomography

Supplementary material

259_2010_1612_MOESM1_ESM.doc (62 kb)
Supplementary Table 1Results of SPM analysis (DOC 61 kb)
259_2010_1612_MOESM2_ESM.doc (66 kb)
Supplementary Table 2Pearson correlation analyses in the AD group (DOC 65 kb)

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Masamichi Yokokura
    • 1
  • Norio Mori
    • 1
  • Shunsuke Yagi
    • 2
  • Etsuji Yoshikawa
    • 3
  • Mitsuru Kikuchi
    • 4
  • Yujiro Yoshihara
    • 1
  • Tomoyasu Wakuda
    • 1
  • Genichi Sugihara
    • 5
  • Kiyokazu Takebayashi
    • 1
  • Shiro Suda
    • 5
  • Yasuhide Iwata
    • 1
  • Takatoshi Ueki
    • 6
  • Kenji J. Tsuchiya
    • 5
  • Katsuaki Suzuki
    • 5
  • Kazuhiko Nakamura
    • 1
  • Yasuomi Ouchi
    • 2
  1. 1.Department of Psychiatry and NeurologyHamamatsu University School of MedicineHamamatsuJapan
  2. 2.Laboratory of Human Imaging Research, Molecular Imaging Frontier Research CenterHamamatsu University School of MedicineHamamatsuJapan
  3. 3.Central Research LaboratoryHamamatsu Photonics K.K.HamamatsuJapan
  4. 4.Department of Psychiatry and Neurobiology, Graduate School of Medical ScienceKanazawa UniversityKanazawaJapan
  5. 5.Research Center for Child Mental DevelopmentHamamatsu University School of MedicineHamamatsuJapan
  6. 6.Department of AnatomyHamamatsu University School of MedicineHamamatsuJapan