Cited by 174Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

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

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Yokokura, Masamichi, Mori, Norio, Yagi, Shunsuke, Yoshikawa, Etsuji, Kikuchi, Mitsuru, Yoshihara, Yujiro, Wakuda, Tomoyasu, Sugihara, Genichi +8 more·2011·European Journal of Nuclear Medicine and Molecular Imaging

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 [(11)C](R)PK11195, [(11)C]PIB and [(18)F]FDG and a battery of cognitive tests within the same day. The binding potentials (BPs) of [(11)C](R)PK11195 were directly compared with those of [(11)C]PIB in the brain regions with reduced glucose metabolism.Results BPs of [(11)C](R)PK11195 and [(11)C]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 [(11)C](R)PK11195 BPs, but not [(11)C]PIB, in the limbic, precuneus and prefrontal regions. Direct comparisons showed a significant negative correlation between [(11)C](R)PK11195 and [(11)C]PIB BPs in the posterior cingulate cortex (PCC) (p < 0.05, corrected) that manifested the most severe reduction in [(18)F]FDG uptake.Conclusion A lack of coupling between microglial activation and amyloid deposits may indicate that Aβ accumulation shown by [(11)C]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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Authors
Yokokura, M., Mori, N., Yagi, S., Yoshikawa, E., Kikuchi, M., Yoshihara, Y., Wakuda, T., Sugihara, G., Takebayashi, K., Suda, S., Iwata, Y., Ueki, T., Tsuchiya, K. J., Suzuki, K., Nakamura, K., & Ouchi, Y.
Affiliations
  • Hamamatsu University School of Medicine (JP)
  • Hamamatsu University (JP)
  • Hamamatsu Photonics (Japan) (JP)
  • Kanazawa University (JP)
Corresponding author
Ouchi, Yasuomi
Venue
European Journal of Nuclear Medicine and Molecular Imaging
Published
2010-09-16
Volume
38
Issue
2
Pages
343-351
ISSN
  • 1619-7070 (ISSN-L)
  • 1619-7089
OpenAlex
W1991282216
Cited by
174
References
42
Citations by year
2026: 4 · 2025: 7 · 2024: 6 · 2023: 9 · 2022: 13 · 2021: 12 · 2020: 13 · 2019: 18 · 2018: 11 · 2017: 17 · 2016: 14 · 2015: 14 · 2014: 10 · 2013: 9 · 2012: 10
FWCI
5.63
Type
journal article
Language
en
Open access
Licence
Locations
  • European Journal of Nuclear Medicine and Molecular Imaging (publishedVersion)
  • PubMed (publishedVersion)
  • HamaMed-Repository (Hamamatsu University School of Medicine) (submittedVersion, cc-by-nc-nd)
Funders
Japan Society for the Promotion of Science (22591260, 23390287, 22591258, 23659562)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, microglial activation, amyloid-beta, hypometabolism, neuroinflammation, PK11195, Pib, FDG-PET, posterior cingulate cortex, early Alzheimer's disease
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Brain, Female, Glucose, Humans, Male, Middle Aged, Neurons, Radioactive Tracers, Case-Control Studies, Amyloid beta-Peptides, Microglia, Positron-Emission Tomography

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