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

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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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Yokokura, Masamichi, Mori, Norio, Yagi, Shunsuke, Yoshikawa, Etsuji, Kikuchi, Mitsuru, Yoshihara, Yujiro, Wakuda, Tomoyasu, Sugihara, Genichi, Takebayashi, Kiyokazu, Suda, Shiro, Iwata, Yasuhide, Ueki, Takatoshi, Tsuchiya, Kenji J., Suzuki, Katsuaki, Nakamura, Kazuhiko, Ouchi, Yasuomi·2011·European Journal of Nuclear Medicine and Molecular Imaging

DOI 10.1007/s00259-010-1612-0

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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
ORCID: Yokokura, Masamichi
Kikuchi, Mitsuru
Yoshihara, Yujiro
Wakuda, Tomoyasu
Sugihara, Genichi
Suda, Shiro
Ueki, Takatoshi
Tsuchiya, Kenji J.
Suzuki, Katsuaki
Nakamura, Kazuhiko
Ouchi, Yasuomi
Venue: European Journal of Nuclear Medicine and Molecular Imaging
Publisher: Springer Science and Business Media LLC
Published: 2010-09-16
Volume: 38
Issue: 2
Pages: 343-351
ISSN: 1619-7070 (ISSN-L)
1619-7089
DOI: 10.1007/s00259-010-1612-0
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: green
hdl.handle.net
Licence: cc-by-nc-nd
www.springer.com/tdm (tdm)
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: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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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In vivo changes in microglial activation and amyloid deposits in brain regions with hypometabolism in Alzheimer’s disease

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