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Front. Aging Neurosci. | doi: 10.3389/fnagi.2018.00304

Involvement of the precuneus/posterior cingulate cortex is significant for the development of Alzheimer’s disease: A PET (THK5351, PiB) and resting fMRI study

 Takamasa Yokoi1,  Hirohisa Watanabe1, 2,  Hiroshi Yamaguchi2,  Epifanio Bagarinao2, Michihito Masuda1, Kazunori Imai1, Aya Ogura1, Reiko Ohdake2, Kazuya Kawabata1, Kazuhiro Hara1, Yuichi Riku1, Shinsuke Ishigaki1,  Masahisa Katsuno1, Shinichi Miyao3, Katsuhiko Kato1, Shinji Naganawa1,  Ryuichi Harada4, Nobuyuki Okamura5,  Kazuhiko Yanai4, Mari Yoshida6 and  Gen Sobue1, 2*
  • 1Nagoya University, Japan
  • 2Brain and Mind Research Center, Nagoya University, Japan
  • 3Meitetsu Hospital, Japan
  • 4Tohoku University, Japan
  • 5Tohoku Medical and Pharmaceutical University, Japan
  • 6Aichi Medical University, Japan

Abstract
Background: Imaging studies in Alzheimer’s disease have yet to answer the underlying questions concerning the relationship among tau retention, neuroinflammation, network disruption, and cognitive decline. We compared the spatial retention patterns of 18F-THK5351 and resting state network disruption in patients with early Alzheimer’s disease and healthy controls.
Methods: We enrolled 23 11C-Pittsburgh compound B (PiB)-positive patients with early Alzheimer’s disease and 24 11C-PiB-negative participants as healthy controls. All participants underwent resting state functional MRI and 18F-THK5351 PET scans. We used scaled subprofile modeling/principal component analysis (SSM/PCA) to reduce the complexity of multivariate data and to identify patterns that exhibited the largest statistical effects (variances) in THK5351 concentration in Alzheimer’s disease and healthy controls.
Findings: SSM/PCA identified a significant spatial THK5351 pattern composed by mainly three clusters including precuneus/posterior cingulate cortex, right and left dorsolateral prefrontal cortex which accounted for 23.6% of the total subject voxel variance of the data and had 82.6% sensitivity and 79.1% specificity in discriminating Alzheimer’s disease from healthy controls. There was a significant relationship between the intensity of the 18F-THK5351 covariation pattern and cognitive scores in Alzheimer’s disease. The spatial patterns of 18F-THK5351 uptake showed significant similarity with intrinsic functional connectivity, especially in the precuneus/posterior cingulate cortex network. Seed-based connectivity analysis from the precuneus/posterior cingulate cortex showed significant decrease in connectivity over widespread brain regions in Alzheimer’s disease patients. An evaluation of an autopsied Alzheimer’s disease patient with Braak V showed that 18F-THK5351 retention corresponded to tau deposition, monoamine oxidase-B and astrogliosis in the precuneus/posterior cingulate cortex.
Interpretation: We identified an Alzheimer’s disease-specific spatial pattern of 18F-THK5351 retention in the precuneus/posterior cingulate cortex, an important connectivity hub region in the brain. Disruption of the functional connections of this important network hub may play an important role in developing dementia in Alzheimer’s disease.

Keywords: 18F-THK5351, 11C-PIB, positron emission tomography (PET), resting state network, MRI, MAO-B, astrocyte

Received: 10 Jul 2018; Accepted: 13 Sep 2018.

Edited by:

Atsushi Takeda, Sendai Nishitaga National Hospital, Japan

Reviewed by:

Eric Tatt Wei Ho, Universiti Teknologi Petronas, Malaysia
TATSUO -. IDO, Neuroscience Research Institute, Gachon University, South Korea  

Copyright: © 2018 Yokoi, Watanabe, Yamaguchi, Bagarinao, Masuda, Imai, Ogura, Ohdake, Kawabata, Hara, Riku, Ishigaki, Katsuno, Miyao, Kato, Naganawa, Harada, Okamura, Yanai, Yoshida and Sobue. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Gen Sobue, Nagoya University, Nagoya, 464-8601, Aichi, Japan, sobueg@med.nagoya-u.ac.jp