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=8) and triple transgenic APP/PS1/tau (3xTg-AD) (n=5) mouse brains. Average μa for control and 3xTg-AD mice was 0.82±0.05 and 0.65±0.05 mm−1, respectively, at 460 nm; and 0.71±0.04 and 0.55±0.04 mm−1, respectively, at 530 nm. Average μs′ for control and 3xTg-AD mice was 1.5±0.1 and 1.7±0.1 mm−1, respectively, at 460 nm; and 1.3±0.1 and 1.5±0.1 mm−1, respectively, at 530 nm. The calculated DPF for control and 3xTg-AD mice was 0.58±0.04 and 0.64±0.04 OD mm, respectively, at 460 nm; and 0.66±0.03 and 0.73±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).