Alzheimer’s disease (AD) has been the leading cause of cognitive impairment and decline in elder individuals. Cross-sectional human studies have reported declined cerebral oxygen metabolism in AD patients tentatively attributed to reduced neuron cells. However, longitudinal change in oxygen metabolism remains unclear. We, therefore, performed a multi-modality (MRI, behavior test, and histology) study on a novel AD mouse model, dubbed as Tau4RΔK-AP, which largely mimics the pathological processes of tau-tangles and amyloid plaques as in human AD. Enhanced oxygen metabolism has been found in Tau4RΔK-AP mice, possibly indicating a compensatory response or an inefficiency of the brain energy consumption.