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. Author manuscript; available in PMC: 2021 Feb 5.
Published in final edited form as: Neuron. 2019 Dec 3;105(3):549–561.e5. doi: 10.1016/j.neuron.2019.10.033

Figure 7. Reduced vascular reactivity in APP/PS1 mice is not associated with local CAA burden, but with loss of vascular smooth muscle cells.

Figure 7.

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 (B). CAA burden was quantified on the maximum intensity projections of the Methoxy-X04 channel and correlated with the amplitude of the evoked vascular reactivity, quantified as the maximum peak at 0.05 Hz in 8–10 months old transgenic mice. No significant correlation was found between CAA burden and evoked vascular reactivity per vessel segment (C; Spearman’s ρ −0.098, p=0.58, n=35 vessel segments in 5 mice). Smooth muscle cell (SMC) density was quantified with ex vivo immunohistochemistry in brain sections of 18 months old wild-type (WT) and Tg mice that underwent in vivo two-photon microscopy. Representative images of pial surface arterioles in WT (D) and Tg (E) mice are shown, which suggest loss of SMCs in CAA-positive vessels. After excluding three vessels that did not exhibit any CAA from the Tg group, SMC density was found to be significantly reduced in Tg (4.9 ± 2.0 %, n=25 vessels in 6 mice) compared to WT mice (7.1 ± 4.1 %, n=34 vessels in 8 mice, t-test, p=0.016) (F). Median and range are indicated in F. * p<0.05.