In vivo positron emission tomography imaging of mitochondrial abnormalities in a mouse model of tauopathy.

Autor: Barron AM; Department of Functional Brain Imaging, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan; Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore. Electronic address: barron@ntu.edu.sg., Ji B; Department of Functional Brain Imaging, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Fujinaga M; Department of Functional Brain Imaging, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Zhang MR; Department of Functional Brain Imaging, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Suhara T; Department of Functional Brain Imaging, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Sahara N; Department of Functional Brain Imaging, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Aoki I; Department of Molecular Imaging and Theranostics, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Tsukada H; Central Research Laboratory, Hamamatsu Photonics K.K., Shizuoka, Japan., Higuchi M; Department of Functional Brain Imaging, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan. Electronic address: higuchi.makoto@qst.go.jp.
Jazyk: angličtina
Zdroj: Neurobiology of aging [Neurobiol Aging] 2020 Oct; Vol. 94, pp. 140-148. Date of Electronic Publication: 2020 May 19.
DOI: 10.1016/j.neurobiolaging.2020.05.003
Abstrakt: Damaged mitochondria may be one of the earliest manifestations of Alzheimer's disease. Because oxidative phosphorylation is a primary source of neuronal energy, unlike glycolysis-dependent energy production in inflamed glia, mitochondrial respiration could provide a selective biomarker of neuronal deterioration in Alzheimer's disease. Here we used a recently developed positron emission tomography (PET) probe targeting mitochondrial complex I (MC-I), 18 F-BCPP-EF, to non-invasively visualize mitochondrial abnormalities in the brains of tau transgenic mice (rTg4510). Tauopathy and neuroinflammation were visualized by PET using a tau probe 11 C-PBB3 and a translocator protein probe, 18 F-FEBMP, respectively. A marked reduction in 18 F-BCPP-EF uptake was observed in hippocampal and forebrain regions of tau transgenic mice, colocalizing with regions of tauopathy, neuronal damage, and neuroinflammation. MC-I signals were highly correlated with atrophy assayed by magnetic resonance imaging, but negatively associated with inflammatory signals, indicating that neuronal metabolic signals measured by MC-I PET were robust to inflammatory interference. MC-I may be a useful imaging biomarker to detect neuronal damage and metabolic changes with minimal interference from concomitant glial hypermetabolism.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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