The effect of cerebral amyloidosis on cerebral hemodynamics was investigated with photoacoustic tomography (PAT) and magnetic resonance imaging (MRI). First, the sensitivity and robustness of PAT for deriving metrics of vascular and tissue oxygenation in the murine brain was assessed in wild-type mice with a hyperoxia-normoxia challenge. Secondly, cerebral oxygenation was assessed in young and aged arcAβ mice and wild-type controls with PAT, while cerebral blood flow (CBF) was determined by perfusion MRI. The investigations revealed that PAT can sensitively and robustly detect physiological changes in vascular and tissue oxygenation. An advanced stage of cerebral amyloidosis in arcAβ mice is accompanied by a decreases in cortical CBF and the cerebral metabolic rate of oxygen (CMRO2), as oxygen extraction fraction (OEF) has been found unaffected. Thus, PAT constitutes a robust non-invasive tool for deriving metrics of tissue oxygenation, extraction and metabolism in the mouse brain under physiological and disease states.