Tatsuhiro Terada1,2, Masamichi Yokokura3, Tomokazu Obi2, Tomoyasu Bunai1, Etsuji Yoshikawa4, Ichiro Ando5, Hitoshi Shimada6, Tetsuya Suhara6, Makoto Higuchi6, Yasuomi Ouchi7. 1. Department of Biofunctional Imaging, Preeminent Medical Photonics Education and Research Center, Hamamatsu University School of Medicine, 1-20-1 Handayama Higashi-ku, Hamamatsu, 431-3192, Japan. 2. Department of Neurology, Shizuoka Institute of Epilepsy and Neurological Disorders, Urushiyama 886, Aoi-ku, Shizuoka, 420-8688, Japan. 3. Department of Psychiatry, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan. 4. Central Research Laboratory, Hamamatsu Photonics KK, 5000 Hirakuchi, Hamakita-ku, Hamamatsu, 4434-0041, Japan. 5. Hamamatsu PET Imaging Center, Hamamatsu Medical Photonics Foundation, Hirakuchi, Hamakita-ku, Hamamatsu, 434-0041, Japan. 6. Department of Functional Brain Imaging Research, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan. 7. Department of Biofunctional Imaging, Preeminent Medical Photonics Education and Research Center, Hamamatsu University School of Medicine, 1-20-1 Handayama Higashi-ku, Hamamatsu, 431-3192, Japan. ouchi@hama-med.ac.jp.
Abstract
OBJECTIVE: Neuronal damage and neuroinflammation are important events occurring in the brain of Alzheimer's disease (AD). The purpose of this study was to clarify in vivo mutual relationships among abnormal tau deposition, neuroinflammation and cognitive impairment in patients with early AD using positron emission tomography (PET) with [11C]PBB3 and [11C]DPA713. METHODS: Twenty patients with early AD and 20 age-matched normal control (NC) subjects underwent a series of PET measurements with [11C]PBB3 for tau aggregation and [11C]DPA713 for microglial activation (neuroinflammation). Inter- and intrasubject comparisons were performed regarding the levels of [11C]PBB3 binding potential (BPND) and [11C]DPA713 BPND in the light of cognitive functions using statistical parametric mapping (SPM) and regions of interest (ROIs) method. RESULTS: The [11C]PBB3 BPND was greater in the temporo-parietal regions of AD patents than NC subjects, and a similar increasing pattern of [11C]DPA713 BPND was observed in the same patients. Correlation analyses within the AD group showed a positive direct correlation between [11C]PBB3 BPND and [11C]DPA713 BPND in the parahippocampus. Pass analysis revealed that cognitive impairment was more likely linked to the level of the parahippocampal [11C]PBB3 BPND than that of [11C]DPA713 BPND. CONCLUSIONS: The pattern of abnormal tau deposition was very similar to that of neuroinflammation in patients with early-stage AD. Specifically, the direct positive correlation of tau pathology with neuroinflammation in the parahippocampus suggests that neuronal damage in this region is closely associated with microglial activation. Consistently, tau aggregation in this region matters more than neuroinflammation regarding the cognitive deterioration in AD.
OBJECTIVE:Neuronal damage and neuroinflammation are important events occurring in the brain of Alzheimer's disease (AD). The purpose of this study was to clarify in vivo mutual relationships among abnormal tau deposition, neuroinflammation and cognitive impairment in patients with early AD using positron emission tomography (PET) with [11C]PBB3 and [11C]DPA713. METHODS: Twenty patients with early AD and 20 age-matched normal control (NC) subjects underwent a series of PET measurements with [11C]PBB3 for tau aggregation and [11C]DPA713 for microglial activation (neuroinflammation). Inter- and intrasubject comparisons were performed regarding the levels of [11C]PBB3 binding potential (BPND) and [11C]DPA713 BPND in the light of cognitive functions using statistical parametric mapping (SPM) and regions of interest (ROIs) method. RESULTS: The [11C]PBB3 BPND was greater in the temporo-parietal regions of AD patents than NC subjects, and a similar increasing pattern of [11C]DPA713 BPND was observed in the same patients. Correlation analyses within the AD group showed a positive direct correlation between [11C]PBB3 BPND and [11C]DPA713 BPND in the parahippocampus. Pass analysis revealed that cognitive impairment was more likely linked to the level of the parahippocampal [11C]PBB3 BPND than that of [11C]DPA713 BPND. CONCLUSIONS: The pattern of abnormal tau deposition was very similar to that of neuroinflammation in patients with early-stage AD. Specifically, the direct positive correlation of tau pathology with neuroinflammation in the parahippocampus suggests that neuronal damage in this region is closely associated with microglial activation. Consistently, tau aggregation in this region matters more than neuroinflammation regarding the cognitive deterioration in AD.
Authors: William C Kreisl; Min-Jeong Kim; Jennifer M Coughlin; Ioline D Henter; David R Owen; Robert B Innis Journal: Lancet Neurol Date: 2020-11 Impact factor: 44.182
Authors: Maura Malpetti; Rogier A Kievit; Luca Passamonti; P Simon Jones; Kamen A Tsvetanov; Timothy Rittman; Elijah Mak; Nicolas Nicastro; W Richard Bevan-Jones; Li Su; Young T Hong; Tim D Fryer; Franklin I Aigbirhio; John T O'Brien; James B Rowe Journal: Brain Date: 2020-05-01 Impact factor: 13.501