Fig. 8: CSF tracer accumulation patterns are variable within PAS of healthy, old, and APP/PS1 mice, and correlate with perivascular MeX04 (i.e., amyloid-β plaque) and ERTR7 (i.e., pial cell) density.

Coronal images demonstrate TxRd tracer accumulation in brains of young, old and APP/PS1 mice (a). The distribution of vessel sizes in young, old and APP/PS1 mice are shown (b) along with the proportion of tracer-positive PAS (c) and tracer positivity according to PAS type (d). Distribution of tracer-positive PAS are further depicted in the three groups according to arterial diameter (e). The overall distribution of tracer mean pixel intensity (MPI) is shown (f) along with distribution of MPI according to PAS type (g); two-way ANOVA with Tukey’s multiple comparisons test. A penetrating arteriole from APP/PS1 mouse is shown at higher power (h) and illustrates diminishment of tracer accumulation below PAS abutting plaques, with brisk fluorescence in secondary penetrating arterioles, possibly representative of regurgitant flow. The distribution of MeX04 (amyloid-β plaque) label according to MPI is summarized in (i). TxRd tracer accumulation (MPI) is summarized in plaque-positive (>1 PAS abutting plaques) versus plaque-negative PAS in (j), showing marked diminishment of tracer accumulation that may be indicative of decreased flow; unpaired t-test. Correlation of MeX04 with ERTR7 pixel are is shown in (k); simple linear regression with 95% CI. Correlation of tracer MPI with ERTR7 label is shown in (l); simple linear regression with 95% CI. Correlation of tracer MPI with MeX04 MPI is shown in (m); simple linear regression with 95% CI. Cyan/CY5, MeX04; blue, lectin; green/FITC, ERTR7; red/Texas Red, TxRd. Scale bars = (a) 500 μm; (h) 50 μm. Data are depicted 30 min following intracisternal tracer infusion. Young: n = 141 vessels from 3 mice; Old: n = 139 vessels from 3 mice; APP/PS1: n = 141 vessels from 3 mice. Source data are provided as a Source Data file.