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

Article type: Research Article

Authors: Nihashi, Takashi^a | Sakurai, Keita^a | Kato, Takashi^{a; b; *} | Iwata, Kaori^b | Kimura, Yasuyuki^b | Ikenuma, Hiroshi^b | Yamaoka, Akiko^c | Takeda, Akinori^c | Arahata, Yutaka^c | Washimi, Yukihiko^c | Suzuki, Keisuke^d | Bundo, Masahiko^e | Sakurai, Takashi^f | Okamura, Nobuyuki^{g; h} | Yanai, Kazuhiko^{g; h} | Ito, Kengoⁱ | Nakamura, Akinori^b | MULNIAD Study Groupⁱ

Affiliations: [a] Department of Radiology, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan | [b] Department of Clinical and Experimental Neuroimaging, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan | [c] Department of Neurology, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan | [d] Innovation Center for Translational Research, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan | [e] Department of Neurosurgery, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan | [f] Center for Comprehensive Care and Research on Memory Disorders, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan | [g] Division of Pharmacology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Aoba Ward, Sendai, Miyagi, Japan | [h] Department of Pharmacology, Tohoku University School of Medicine, Aoba-ku, Sendai, Miyagi, Japan | [i] National Center for Geriatrics and Gerontology, Obu, Aichi, Japan

Correspondence: [*] Correspondence to: Takashi Kato, MD, PhD, Department of Radiology/Clinical and Experimental Neuroimaging, National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu City, Aichi Prefecture, 474-8511, Japan. Tel.: +81 562 46 2311; E-mail: tkato@ncgg.go.jp.

Abstract: Background: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. Objective: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. Methods: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. Results: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. Conclusion: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.

Keywords: Alzheimer’s disease, amyloid, Braak stages, ¹⁸F-THK5351, positron emission tomography

DOI: 10.3233/JAD-215024

Journal: Journal of Alzheimer's Disease, vol. 85, no. 1, pp. 223-234, 2022