Association between Aβ and tau accumulations and their influence on clinical features in aging and Alzheimer's disease spectrum brains: A [11C]PBB3-PET study

Hitoshi Shimada; Soichiro Kitamura; Hitoshi Shinotoh; Hironobu Endo; Fumitoshi Niwa; Shigeki Hirano; Yasuyuki Kimura; Ming-Rong Zhang; Satoshi Kuwabara; Tetsuya Suhara; Makoto Higuchi

doi:10.1016/j.dadm.2016.12.009

Association between Aβ and tau accumulations and their influence on clinical features in aging and Alzheimer's disease spectrum brains: A [¹¹C]PBB3-PET study

Alzheimers Dement (Amst). 2016 Dec 22:6:11-20. doi: 10.1016/j.dadm.2016.12.009. eCollection 2017.

Authors

Affiliations

¹ Department of Functional Brain Imaging Research (DOFI), Clinical Research Cluster, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), Chiba-shi, Chiba, Japan.
² Department of Functional Brain Imaging Research (DOFI), Clinical Research Cluster, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), Chiba-shi, Chiba, Japan; Neurology Chiba Clinic, Chiba-shi, Chiba, Japan.
³ Department of Functional Brain Imaging Research (DOFI), Clinical Research Cluster, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), Chiba-shi, Chiba, Japan; Division of Neurology, Kobe University Graduate School of Medicine, Kobe-shi, Hyogo, Japan.
⁴ Department of Functional Brain Imaging Research (DOFI), Clinical Research Cluster, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), Chiba-shi, Chiba, Japan; Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto-shi, Kyoto, Japan.
⁵ Department of Functional Brain Imaging Research (DOFI), Clinical Research Cluster, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), Chiba-shi, Chiba, Japan; Department of Neurology, Graduate School of Medicine, Chiba University, Chiba-shi, Chiba, Japan.
⁶ Department of Radiopharmaceuticals Development, Clinical Research Cluster, NIRS, QST, Chiba-shi, Chiba, Japan.
⁷ Department of Neurology, Graduate School of Medicine, Chiba University, Chiba-shi, Chiba, Japan.

Abstract

Introduction: Amyloid-β (Aβ) and tau accumulations may occur independently and concurrently as exemplified by primary age-related tauopathy and Alzheimer's disease (AD), respectively. Interactions between Aβ and tau accumulations and their influence on clinical features, however, are still unclear.

Methods: Associations among clinical symptoms, gray-matter volume, regional tau, and Aβ deposition assessed by positron emission tomography with [¹¹C]pyridinyl-butadienyl-benzothiazole 3 (PBB3) and [¹¹C]Pittsburgh compound-B (PiB), were evaluated in 17 AD, 9 mild cognitive impairment due to AD, and 28 PiB(-)-cognitive healthy controls (HCs).

Results: High tau burden was associated with aging and low-level education in PiB(-)-HC and AD-spectrum groups, and with high Aβ burden and low-level education in all subjects. It was not Aβ but tau accumulation that showed significant associations with cognitive performance even in PiB(-)-HC.

Discussion: The present study indicated aging and low-level education after Aβ would be enhancers for tau pathology, associated with neurodegeneration and cognitive impairment in healthy and diseased elderly individuals.

Keywords: Aging; Alzheimer's disease; Amyloid; Biomarkers; Brain atrophy; Cognitive decline; Cognitive reserve; Dementia; MCI; Positron emission tomography; Preclinical; Tau; [11C]PBB3; [11C]PiB.