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

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), 18F-BCPP-EF, to non-invasively visualize mito-chondrial abnormalities in the brains of tau transgenic mice (rTg4510). Tauopathy and neuro-inflammation were visualized by PET using a tau probe C-11-PBB3 and a translocator protein probe, F-18-FEBMP, respectively. A marked reduction in F-18-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. (C) 2020 Elsevier Inc. All rights reserved.