BRAIN and NERVE Shinkei Kenkyu no Shinpo Volume 69, Issue 7 (July 2017)

Tau Positron Emission Tomography Makoto Higuchi 1 1National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology Keyword: ポジトロンエミッション断層撮影 , イメージング , タウ , アルツハイマー病 , 前頭側頭葉変性症 , positron emission tomography , imaging , tau , Alzheimer's disease , frontotemporal lobar degeneration pp.819-823
Published Date 2017/7/1
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Accumulation of fibrillar tau protein aggregates is a neuropathological hallmark of Alzheimer's disease (AD) and related neurodegenerative dementias, including a subgroup of frontotemporal lobar degeneration (FTLD). Visualization of tau lesions in the brains of living subjects enables a pathology-based diagnosis of dementing illnesses in the prodromal stage, and offers objective measures of disease progression and outcomes of disease-modifying therapies. With this rationale, diverse classes of low-molecular-weight chemicals capable of binding to a β-pleated sheet structure have been developed to be used for in vivo positron emission tomography (PET) of tau pathologies. Clinical PET studies of AD patients with such tau probes have provided the following insights: (1) Tau fibrils accumulate in the hippocampal formation in an age-dependent manner that is independent of amyloid-beta peptide (Aβ) pathology; (2) The deposition of Aβ may trigger a spatial expansion of tau pathology, in transition from normal aging to advanced AD; and (3) Tau accumulation is intimately associated with local neuronal loss, leading to cortical atrophy and focal symptoms. In contrast, studies of FTLD have shown a limited performance of first-generation PET probes in capturing non-AD-type tau lesions. New compounds have accordingly been developed and clinically tested, proving to yield a high contrast for tau deposits with high specificity. These second-generation probes are being evaluated primarily by pharmaceutical companies, in line with their growing demands for neuroimaging-based biomarkers serving for clinical trials of anti-Aβ and anti-tau therapies. Meanwhile, a consortium flexibly linking academia and industry to facilitate the utilization of research tools, including tau PET probes, has been established in Japan, for the ultimate purpose of elucidating the molecular etiology of tauopathies and creating diagnostic and therapeutic agents based on such an understanding.

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BRAIN and NERVE-神経研究の進歩
69巻7号 (2017年7月)
電子版ISSN 1344-8129 印刷版ISSN 1881-6096 医学書院