Decreased cerebral metabolic rate of oxygen (CMRO2) is associated with increased tau deposition in Alzheimer's disease.

INTRODUCTION: Transgenic Alzheimer's (AD) mouse models and post mortem studies have shown that tau pathology disrupts the mitochondrial electron transport chain and results in mitochondrial damage and synaptic dysfunction. We assessed whether magnetic resonance imaging (MRI)-derived measures of oxygen metabolism, oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) were associated with tau deposition in vivo. METHODS: We assessed tau using 18F-MK-6240 positron emission tomography and CMRO2/OEF using multi-echo gradient-recalled echo with QQ processing, as well as pseudo-continuous arterial spin-labeling MRI in cognitively normal (CN) elderly and subjects with mild cognitive impairment/AD (N = 42). Associations among imaging measures were evaluated across cortical lobes, including comparisons between regions with and without tau deposition. RESULTS: Across all subjects, higher tau standardized uptake value ratio (SUVR) was associated with lower cerebral blood flow (CBF) and CMRO2. Tau SUVR was negatively associated with Montreal Cognitive Assessment scores, whereas OEF, CBF, and CMRO2 were positively associated. Within subjects, CMRO2 was lower in tau-positive temporal regions in both CN and MCI/AD subjects, and CBF was lower in tau-positive temporal regions in CN subjects. DISCUSSION: MRI-derived CBF and CMRO2 were associated with regional tau deposition, particularly in the temporal lobe, which suggests they have potential as non-invasive markers of metabolic alterations accompanying tau pathology.