title: Longitudinal Assessment of Tau Pathology in Patients with Alzheimer's Disease Using [18F]THK-5117 Positron Emission Tomography.
abstract: 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.
authors.affiliation: Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Tohoku University, Sendai city, Miyagi prefecture, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Ishiki
authors.affiliation: Department of Pharmacology, Tohoku University School of Medicine, Sendai city, Miyagi prefecture, Japan; Division of Neuro-imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai city, Miyagi prefecture, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Okamura
authors.affiliation: Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Tohoku University, Sendai city, Miyagi prefecture, Japan.
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Furukawa
authors.affiliation: Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai city, Miyagi prefecture, Japan.
authors.forename: Shozo
authors.initials: S
authors.lastname: Furumoto
authors.affiliation: Division of Neuro-imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai city, Miyagi prefecture, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Harada
authors.affiliation: Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Tohoku University, Sendai city, Miyagi prefecture, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Tomita
authors.affiliation: Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai city, Miyagi prefecture, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Hiraoka
authors.affiliation: Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai city, Miyagi prefecture, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Watanuki
authors.affiliation: Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai city, Miyagi prefecture, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ishikawa
authors.affiliation: Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai city, Miyagi prefecture, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Tago
authors.affiliation: Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai city, Miyagi prefecture, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Funaki
authors.affiliation: Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai city, Miyagi prefecture, Japan.
authors.forename: Ren
authors.initials: R
authors.lastname: Iwata
authors.affiliation: Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai city, Miyagi prefecture, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Tashiro
authors.affiliation: Department of Pharmacology, Tohoku University School of Medicine, Sendai city, Miyagi prefecture, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yanai
authors.affiliation: Division of Neuro-imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai city, Miyagi prefecture, Japan; Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai city, Miyagi prefecture, Japan.
authors.forename: Yukitsuka
authors.initials: Y
authors.lastname: Kudo
authors.affiliation: Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Tohoku University, Sendai city, Miyagi prefecture, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000473:pathology*; D000814:Aniline Compounds; D016022:Case-Control Studies; D003710:Demography; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D049268:Positron-Emission Tomography; D011804:Quinolines; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C000604726:6-((3-fluoro-2-hydroxy)propoxy)-2-(4-methylaminophenyl)quinoline; D000814:Aniline Compounds; D011804:Quinolines; D016875:tau Proteins