Representative in vivo two-photon microscopy image of a fluorescent angiogram through a cranial window in an awake head-fixed transgenic (Tg) APP/PS1 mouse (A). Intraparenchymal Aβ plaques and vascular Aβ depositions (CAA) are visualized through Methoxy-X04, an intraperitoneally injected fluorescent Congo Red derivative that crosses the blood-brain barrier and binds to Aβ. Note: fluorescein dextran is depicted in red for better contrast with Aβ in cyan. Spontaneous vasomotion in Tg mice is recorded in arterioles over a 5-minute time course at 2x magnification and a frame rate of ~2 Hz (B), and is comparable to wild-type (WT) animals (D; maximum amplitude at 0.1 Hz was 0.0094 ± 0.0083 1/Hz in Tg (n=13 vessels in 4 mice) vs. 0.014 ± 0.010 1/Hz in WT mice (n=14 vessels in 8 mice), t-test, p=0.29). The combined Fourier plot shows the averaged frequency distributions (after averaging several ROIs per vessel) in the range 0.02 – 0.5 Hz for WT and Tg mice (C). Note: three vessel measurements from Tg mice were excluded from the averaged plot because no peaks were observed <0.5 Hz. Paravascular clearance decay curves are comparable between WT (n=12 vessels in 8 mice) and Tg mice (n=11 vessels in 4 mice) (E), quantified as area under the curve (F; 839 ± 341 in WT vs. 908 ± 510 in Tg, t-test, p=0.70). Shaded areas in C and error bars in E represent standard error of the mean. Median and range are indicated in D and F.