Abstract. Baseline optical properties are typically assumed in calculating the differential pathlength factor (DPF) of mouse brains, a value used in the modified Beer-Lambert law to characterize an evoked stimulus response. We used spatial frequency domain imaging to measure in vivo baseline optical properties in 20-month-old control (n ¼ 8) and triple transgenic APP/PS1/tau (3xTg-AD) (n ¼ 5) mouse brains. Average μ a for control and 3xTg-AD mice was 0.82 AE 0.05 and 0.65 AE 0.05 mm −1 , respectively, at 460 nm; and 0.71 AE 0.04 and 0.55 AE 0.04 mm −1 , respectively, at 530 nm. Average μ 0 s for control and 3xTg-AD mice was 1.5 AE 0.1 and 1.7 AE 0.1 mm −1 , respectively, at 460 nm; and 1.3 AE 0.1 and 1.5 AE 0.1 mm −1 , respectively, at 530 nm. The calculated DPF for control and 3xTg-AD mice was 0.58 AE 0.04 and 0.64 AE 0.04 OD mm, respectively, at 460 nm; and 0.66 AE 0.03 and 0.73 AE 0.05 OD mm, respectively, at 530 nm. In hindpaw stimulation experiments, the hemodynamic increase in brain tissue concentration of oxyhemoglobin was threefold larger and two times longer in the control mice compared to 3xTg-AD mice. Furthermore, the washout of deoxyhemoglobin from increased brain perfusion was seven times larger in controls compared to 3xTg-AD mice (p < 0.05).