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Fig. 5 | Acta Neuropathologica Communications

Fig. 5

From: Cerebral amyloid angiopathy aggravates perivascular clearance impairment in an Alzheimer’s disease mouse model

Fig. 5

Early decrease in the perivascular CSF influx and gradual deterioration in APP/PS1 mice. a Schematic illustration of the cisterna magna (CM) injection and perfusion schedule. b Representative image of brain injected 3-kDa FITC-dextran (3 k-FITC) and 40-kDa TMR-dextran (40 k-TMR) via the cisterna magna. Scale bar = 100 µm. c, d Quantification of the CSF influx signal in 3 k-FITC (c) and 40 k-TMR (d). 3 k-FITC [p < 0.0001 (age), p = 0.0002 (genotype)]; 40 k-TMR [p < 0.0001 (age*genotype interaction), p < 0.0001 (age)]. e Quantification of the number of penetrating vessels with 3 k-FITC and 40 k-TMR signals. Note that the number of penetrating vessels with 3 k-FITC and 40 k-TMR decreases in the mid Tg and further decreases in old Tg. [p < 0.0001 (age), p < 0.0001 (genotype), p < 0.0001(age*genotype interaction)]. f Schematic illustration of the linearized cortical region of interest. Starting from the black mid-line, the cortex is linearized in the direction of the black dotted arrow (upper). The blue line represents the movement of CSF. D: dorsal, L: lateral, V: ventral, R: right, L: left. g Representative images of perivascular CSF influx within the brain cortex. Perivascular CSF influx was discovered along the penetrating vessels (white arrowheads). Note that the overall influx signal is increased in old Tg; however, the perivascular-specific signal is reduced. Scale bar = 100 µm. h, i. Regional differences in the CSF influx signal across the brain cortex in 3 k-FITC (h) and 40 k-TMR (i). 3 k-FITC {[ventral (p < 0.0001(age*genotype interaction), p < 0.0001 (age), p < 0.0001 (genotype)]; [lateral (p = 0.0001 (age*genotype interaction), p < 0.0001(age), p < 0.0001(genotype)]; [dorsal (p < 0.0001 (age*genotype interaction), p < 0.0001(age), p < 0.0001(genotype)]}. 40 k-TMR {[ventral (p < 0.0001(age); lateral (p < 0.0001 (age*genotype interaction), p < 0.0001(age)]; [dorsal (p = 0.0015 (age*genotype interaction), p < 0.0001(age)]}. j Representative images of tracer distribution in perivascular CSF influx. The 3 k-FITC is distributed along the arteries and capillaries in Wt (white arrowhead), but is not observed in the capillaries of Tg. Note that distribution of 3 k-FITC is disrupted in old Tg. Scale bar = 100 µm k. Representative images of the glia limitans around the pia mater and vessels. Astrocyte and amyloid plaque are identified using GFAP and MX04, respectively. Astrocytes (GFAP) are densely packed around the pia mater (white asterisk) and vessels (yellow arrowhead). Note that the astrocytes (GFAP) have almost disappeared around the vessels and are located around the parenchymal plaque in old Tg. Astrocytes are observed rarely around blood vessels with excessive amyloid deposition (yellow line arrowhead). Scale bar = 100 µm. (mid Wt = 9, mid Tg = 9, old Wt = 8, old Tg = 8, 7 slices/mouse). All data are presented as the mean ± SEM. ** p < 0.01, *** p < 0.001, **** p < 0.0001, two-way ANOVA with Bonferroni’s post hoc test

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