TY - JOUR
T1 - Longitudinal assessment of Tau pathology in patients with Alzheimer's disease using [18F] THK-5117 positron emission tomography
AU - Ishiki, Aiko
AU - Okamura, Nobuyuki
AU - Furukawa, Katsutoshi
AU - Furumoto, Shozo
AU - Harada, Ryuichi
AU - Tomita, Naoki
AU - Hiraoka, Kotaro
AU - Watanuki, Shoichi
AU - Ishikawa, Yoichi
AU - Tago, Tetsuro
AU - Funaki, Yoshihito
AU - Iwata, Ren
AU - Tashiro, Manabu
AU - Yanai, Kazuhiko
AU - Kudo, Yukitsuka
AU - Arai, Hiroyuki
N1 - Funding Information:
The authors have read the journal's policy and the authors of this manuscript have the following competing interests: YK, NO, and SF received research grants from GE Healthcare. YK also received research grants from Sumitomo Electric Industries. YK and NO own stock in Clino Ltd. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.
Publisher Copyright:
© 2015 Ishiki et al This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2015/10/13
Y1 - 2015/10/13
N2 - The formation of neurofibrillary tangles is believed to contribute to the neurodegeneration observed in Alzheimer's disease (AD). Postmortem studies have shown strong associations between the neurofibrillary pathology and both neuronal loss and the severity of cognitive impairment. However, the temporal changes in the neurofibrillary pathology and its association with the progression of the disease are not well understood. Tau positron emission tomography (PET) imaging is expected to be useful for the longitudinal assessment of neurofibrillary pathology in the living brain. Here, we performed a longitudinal PET study using the tau-selective PET tracer [18F]THK-5117 in patients with AD and in healthy control subjects. Annual changes in [18F]THK-5117 binding were significantly elevated in the middle and inferior temporal gyri and in the fusiform gyrus of patients with AD. Compared to patients with mild AD, patients with moderate AD showed greater changes in the tau load that were more widely distributed across the cortical regions. Furthermore, a significant correlation was observed between the annual changes in cognitive decline and regional [18F] THK-5117 binding. These results suggest that the cognitive decline observed in patients with AD is attributable to the progression of neurofibrillary pathology. Longitudinal assessment of tau pathology will contribute to the assessment of disease progression and treatment efficacy.
AB - The formation of neurofibrillary tangles is believed to contribute to the neurodegeneration observed in Alzheimer's disease (AD). Postmortem studies have shown strong associations between the neurofibrillary pathology and both neuronal loss and the severity of cognitive impairment. However, the temporal changes in the neurofibrillary pathology and its association with the progression of the disease are not well understood. Tau positron emission tomography (PET) imaging is expected to be useful for the longitudinal assessment of neurofibrillary pathology in the living brain. Here, we performed a longitudinal PET study using the tau-selective PET tracer [18F]THK-5117 in patients with AD and in healthy control subjects. Annual changes in [18F]THK-5117 binding were significantly elevated in the middle and inferior temporal gyri and in the fusiform gyrus of patients with AD. Compared to patients with mild AD, patients with moderate AD showed greater changes in the tau load that were more widely distributed across the cortical regions. Furthermore, a significant correlation was observed between the annual changes in cognitive decline and regional [18F] THK-5117 binding. These results suggest that the cognitive decline observed in patients with AD is attributable to the progression of neurofibrillary pathology. Longitudinal assessment of tau pathology will contribute to the assessment of disease progression and treatment efficacy.
UR - http://www.scopus.com/inward/record.url?scp=84948738866&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84948738866&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0140311
DO - 10.1371/journal.pone.0140311
M3 - Article
C2 - 26461913
AN - SCOPUS:84948738866
SN - 1932-6203
VL - 10
JO - PLoS ONE
JF - PLoS ONE
IS - 10
M1 - e0140311
ER -