In vivo changes in microglial activation and amyloid deposits in brain regions with hypometabolism in Alzheimer’s disease
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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.
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.
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.
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.
KeywordsAlzheimer’s disease Microglia Amyloid β protein Positron emission tomography
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
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