Patterns of Distribution of 18F-THK5351 Positron Emission Tomography in Alzheimer's Disease Continuum

Alzheimer's disease (AD) is conceptualized as a biological continuum encompassing the preclinical (clinically asymptomatic but with evidence of AD pathology) and clinical (symptomatic) phases. Using 18F-THK5351 as a tracer that binds to both tau and monoamine oxidase B (MAO-B), we investigated...

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Published inJournal of Alzheimer's disease Vol. 85; no. 1; p. 223
Main Authors Nihashi, Takashi, Sakurai, Keita, Kato, Takashi, Iwata, Kaori, Kimura, Yasuyuki, Ikenuma, Hiroshi, Yamaoka, Akiko, Takeda, Akinori, Arahata, Yutaka, Washimi, Yukihiko, Suzuki, Keisuke, Bundo, Masahiko, Sakurai, Takashi, Okamura, Nobuyuki, Yanai, Kazuhiko, Ito, Kengo, Nakamura, Akinori
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LanguageEnglish
Published Netherlands 04.01.2022
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Abstract Alzheimer's disease (AD) is conceptualized as a biological continuum encompassing the preclinical (clinically asymptomatic but with evidence of AD pathology) and clinical (symptomatic) phases. Using 18F-THK5351 as a tracer that binds to both tau and monoamine oxidase B (MAO-B), we investigated the changes in 18F-THK5351 accumulation patterns in AD continuum individuals with positive amyloid PET consisting of cognitively normal individuals (CNp), amnestic mild cognitive impairment (aMCI), and AD and cognitively normal individuals (CNn) with negative amyloid PET. We studied 69 individuals (32 CNn, 11 CNp, 9 aMCI, and 17 AD) with structural magnetic resonance imaging, 11C-Pittsburgh compound-B (PIB) and 18F-THK5351 PET, and neuropsychological assessment. 18F-THK5351 accumulation was evaluated with visual analysis, voxel-based analysis and combined region of interest (ROI)-based analysis corresponding to Braak neurofibrillary tangle stage. On visual analysis, 18F-THK5351 accumulation was increased with stage progression in the AD continuum. On voxel-based analysis, there was no statistical difference in 18F-THK5351 accumulation between CNp and CNn. However, a slight increase of the bilateral posterior cingulate gyrus in aMCI and definite increase of the bilateral parietal temporal association area and posterior cingulate gyrus/precuneus in AD were detected compared with CNn. On ROI-based analyses, 18F-THK5351 accumulation correlated positively with supratentorial 11C-PIB accumulation and negatively with the hippocampal volume and neuropsychological assessment. The AD continuum showed an increase in 18F-THK5351 with stage progression, suggesting that 18F-THK5351 has the potential to visualize the severity of tau deposition and neurodegeneration in accordance with the AD continuum.
AbstractList Alzheimer's disease (AD) is conceptualized as a biological continuum encompassing the preclinical (clinically asymptomatic but with evidence of AD pathology) and clinical (symptomatic) phases. Using 18F-THK5351 as a tracer that binds to both tau and monoamine oxidase B (MAO-B), we investigated the changes in 18F-THK5351 accumulation patterns in AD continuum individuals with positive amyloid PET consisting of cognitively normal individuals (CNp), amnestic mild cognitive impairment (aMCI), and AD and cognitively normal individuals (CNn) with negative amyloid PET. We studied 69 individuals (32 CNn, 11 CNp, 9 aMCI, and 17 AD) with structural magnetic resonance imaging, 11C-Pittsburgh compound-B (PIB) and 18F-THK5351 PET, and neuropsychological assessment. 18F-THK5351 accumulation was evaluated with visual analysis, voxel-based analysis and combined region of interest (ROI)-based analysis corresponding to Braak neurofibrillary tangle stage. On visual analysis, 18F-THK5351 accumulation was increased with stage progression in the AD continuum. On voxel-based analysis, there was no statistical difference in 18F-THK5351 accumulation between CNp and CNn. However, a slight increase of the bilateral posterior cingulate gyrus in aMCI and definite increase of the bilateral parietal temporal association area and posterior cingulate gyrus/precuneus in AD were detected compared with CNn. On ROI-based analyses, 18F-THK5351 accumulation correlated positively with supratentorial 11C-PIB accumulation and negatively with the hippocampal volume and neuropsychological assessment. The AD continuum showed an increase in 18F-THK5351 with stage progression, suggesting that 18F-THK5351 has the potential to visualize the severity of tau deposition and neurodegeneration in accordance with the AD continuum.
Author Arahata, Yutaka
Takeda, Akinori
Yamaoka, Akiko
Okamura, Nobuyuki
Iwata, Kaori
Sakurai, Keita
Sakurai, Takashi
Kimura, Yasuyuki
Nihashi, Takashi
Washimi, Yukihiko
Bundo, Masahiko
Ikenuma, Hiroshi
Yanai, Kazuhiko
Suzuki, Keisuke
Ito, Kengo
Nakamura, Akinori
Kato, Takashi
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  fullname: Okamura, Nobuyuki
  organization: Department of Pharmacology, Tohoku University School of Medicine, Aoba-ku, Sendai, Miyagi, Japan
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  givenname: Kazuhiko
  surname: Yanai
  fullname: Yanai, Kazuhiko
  organization: Department of Pharmacology, Tohoku University School of Medicine, Aoba-ku, Sendai, Miyagi, Japan
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  givenname: Kengo
  surname: Ito
  fullname: Ito, Kengo
  organization: National Center for Geriatrics and Gerontology, Obu, Aichi, Japan
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  givenname: Akinori
  surname: Nakamura
  fullname: Nakamura, Akinori
  organization: Department of Clinical and Experimental Neuroimaging, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan
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Keywords Braak stages
amyloid
Alzheimer’s disease
positron emission tomography
18F-THK5351
Language English
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SubjectTerms Aged
Alzheimer Disease - diagnosis
Alzheimer Disease - metabolism
Aminopyridines
Amnesia - diagnostic imaging
Amnesia - metabolism
Aniline Compounds
Brain - diagnostic imaging
Brain - metabolism
Cognitive Dysfunction - diagnostic imaging
Cognitive Dysfunction - metabolism
Disease Progression
Female
Fluorodeoxyglucose F18
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Neuropsychological Tests
Positron-Emission Tomography
Quinolines
Radiopharmaceuticals
Severity of Illness Index
tau Proteins - metabolism
Thiazoles
Title Patterns of Distribution of 18F-THK5351 Positron Emission Tomography in Alzheimer's Disease Continuum
URI https://www.ncbi.nlm.nih.gov/pubmed/34776443
Volume 85
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