Fig. 3.

Association of albumin leak and endothelial junctions with SGP + vascular cells after plaque formation. A Representative image of SGP⁺ EC (green) localized to a capillary leak of endogenous albumin is indicated by dashed yellow box. Amyloid plaques were observed in 8-month-old APP/PS1 mice (white dashed lines). Claudin-5 (cyan) and VE-cadherin (red) expression appear to be reduced and disorganized, respectively. B Representative image of SGP⁺ perivascular cell (green) localized to large vessel leak of endogenous albumin. No leak was observed in similar vessel in WT mice. C Albumin leak was found more in large and small blood vessels (BV) in older APP/PS1 mice (red) compared to wildtype (WT) mice (blue). D Global Claudin-5 expression was significantly reduced in APP/PS1 mice compared to WT mice. E VE-cadherin was not significantly altered between 8-month-old WT and APP/PS1 mice. F Positive correlation of number of SGP⁺ cells within 50 microns to leak area in 8-month-old APP/PS1 mice. Gi Staining of blood vessels positive for CD31 (red) and senescence marker p21 (green) and nuclei (DAPI, blue) in post-mortem human mid-temporal cortical sections. Senescence of endothelial cells and perivascular cells were detected in human Alzheimer’s disease (AD) brain sections (white arrows). Gii Human brain sections had decreased expression of VE-cadherin (green) in blood vessels positive for CD31 (red). Giii Overall expression of VE-cadherin in human AD mid-temporal region. Mouse data is from 3 independent experiments; human data is from 3 non-demented controls and 3 AD age and sex-matched cases. All data are represented as mean ± standard deviation. Unpaired t-test was used to determine leak number per section, VE-cadherin, and claudin-5 expression between WT and APP/PS1 mice. *p-value ≤ 0.05, WT = 4–6, and APP/PS1 = 5–7 mice. Scale bar in Fig. A = 10 µm, Fig. Gi = 10 µm and Gii = 20 µm