TY - JOUR
T1 - Involvement of the precuneus/posterior cingulate cortex is significant for the development of Alzheimer's disease
T2 - A PET (THK5351, PiB) and resting fMRI study
AU - Yokoi, Takamasa
AU - Watanabe, Hirohisa
AU - Yamaguchi, Hiroshi
AU - Bagarinao, Epifanio
AU - Masuda, Michihito
AU - Imai, Kazunori
AU - Ogura, Aya
AU - Ohdake, Reiko
AU - Kawabata, Kazuya
AU - Hara, Kazuhiro
AU - Riku, Yuichi
AU - Ishigaki, Shinsuke
AU - Katsuno, Masahisa
AU - Miyao, Shinichi
AU - Kato, Katsuhiko
AU - Naganawa, Shinji
AU - Harada, Ryuichi
AU - Okamura, Nobuyuki
AU - Yanai, Kazuhiko
AU - Yoshida, Mari
AU - Sobue, Gen
N1 - Publisher Copyright:
© 2018 Yokoi, Watanabe, Yamaguchi, Bagarinao, Masuda, Imai, Ogura, Ohdake, Kawabata, Hara, Riku, Ishigaki, Katsuno, Miyao, Kato, Naganawa, Harada, Okamura, Yanai, Yoshida and Sobue.
PY - 2018/10/5
Y1 - 2018/10/5
N2 - Background: Imaging studies in Alzheimer's disease (AD) 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 (RSN) disruption in patients with early AD and healthy controls. Methods: We enrolled 23 11C-Pittsburgh compound B (PiB)-positive patients with early AD 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 AD and healthy controls. Findings: SSM/PCA identified a significant spatial THK5351 pattern composed by mainly three clusters including precuneus/posterior cingulate cortex (PCC), right and left dorsolateral prefrontal cortex (DLPFC) 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 AD from healthy controls. There was a significant relationship between the intensity of the 18F-THK5351 covariation pattern and cognitive scores in AD. The spatial patterns of 18F-THK5351 uptake showed significant similarity with intrinsic functional connectivity, especially in the PCC network. Seed-based connectivity analysis from the PCC showed significant decrease in connectivity over widespread brain regions in AD patients. An evaluation of an autopsied AD patient with Braak V showed that 18F-THK5351 retention corresponded to tau deposition, monoamine oxidase-B (MAO-B) and astrogliosis in the precuneus/PCC. Interpretation: We identified an AD-specific spatial pattern of 18F-THK5351 retention in the precuneus/PCC, 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 AD.
AB - Background: Imaging studies in Alzheimer's disease (AD) 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 (RSN) disruption in patients with early AD and healthy controls. Methods: We enrolled 23 11C-Pittsburgh compound B (PiB)-positive patients with early AD 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 AD and healthy controls. Findings: SSM/PCA identified a significant spatial THK5351 pattern composed by mainly three clusters including precuneus/posterior cingulate cortex (PCC), right and left dorsolateral prefrontal cortex (DLPFC) 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 AD from healthy controls. There was a significant relationship between the intensity of the 18F-THK5351 covariation pattern and cognitive scores in AD. The spatial patterns of 18F-THK5351 uptake showed significant similarity with intrinsic functional connectivity, especially in the PCC network. Seed-based connectivity analysis from the PCC showed significant decrease in connectivity over widespread brain regions in AD patients. An evaluation of an autopsied AD patient with Braak V showed that 18F-THK5351 retention corresponded to tau deposition, monoamine oxidase-B (MAO-B) and astrogliosis in the precuneus/PCC. Interpretation: We identified an AD-specific spatial pattern of 18F-THK5351 retention in the precuneus/PCC, 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 AD.
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U2 - 10.3389/fnagi.2018.00304
DO - 10.3389/fnagi.2018.00304
M3 - Article
AN - SCOPUS:85055318776
SN - 1663-4365
VL - 10
JO - Frontiers in Aging Neuroscience
JF - Frontiers in Aging Neuroscience
IS - OCT
M1 - 304
ER -