Longitudinal Assessment of Tau Pathology in Patients with Alzheimer's Disease Using [18F]THK-5117 Positron Emission Tomography.

Aiko Ishiki,Naoki Tomita,Ren Iwata,Shoichi Watanuki,Katsutoshi Furukawa,Yukitsuka Kudo,Manabu Tashiro,Hiroyuki Arai,Shozo Furumoto,Nobuyuki Okamura,Yoichi Ishikawa,Tetsuro Tago,Ryuichi Harada,Kotaro Hiraoka,Kazuhiko Yanai,Yoshihito Funaki,Stephen D Ginsberg

doi:10.1371/journal.pone.0140311

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.

Highlights

The increasing age of the population is leading to an increase in the prevalence of dementia
Significant differences between healthy controls (HCs) and patients with Alzheimer’s disease (AD) were observed for the Mini Mental State Examination (MMSE) scores and Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAScog) scores at baseline
Representative [18F]THK-5117 positron emission tomography (PET) images at baseline and follow-up are shown in Fig 1. [18F]THK-5117 retention in the anterior and inferior temporal regions is evident in the patient with AD (87-year-old man, MMSE score: 25) at baseline, while it is not evident in the HC participant (78-year-old man, MMSE score: 30) at baseline

Summary

Introduction

The increasing age of the population is leading to an increase in the prevalence of dementia. Alzheimer’s disease (AD), the most common cause of dementia, is neuropathologically defined by two characteristic protein deposits in the brain: senile plaques and neurofibrillary tangles (NFTs) [1]. Senile plaques are composed of extracellular aggregates of amyloid-β (Aβ) protein, while NFTs are composed of twisted filaments, termed paired helical filaments, of hyperphosphorylated tau protein [2]. According to the amyloid cascade hypothesis [3], the accumulation of Aβ is a primary feature of AD, which is followed by the accumulation of NFTs and eventually neuronal death. Both Aβ and tau are excellent targets for developing treatments for AD

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Conclusion