BACKGROUND: signalling pathway might influence cSVD-related pathology. METHODS: signalling and characterised these mice using different imaging and staining techniques, as well as behaviour tests measuring cognition in adult and aged mice. Immunoblots, electrophysiology, perfusion measurements, and in vitro experiments complemented those techniques. FINDINGS: signalling led to capillary rarefaction and blood-brain barrier disruption in aged mice. These effects were accompanied by disturbed VEGF signalling and an increase in senescence markers and oxidative stress in the vasculature, culminating in cognitive impairment with increased tau phosphorylation in the cortex and hippocampus and decreased myelination in the white matter. INTERPRETATION: in endothelial cells in ageing. Furthermore, our results show that the combination of cerebral endothelial dysfunction and ageing accelerates cognitive impairment. FUNDING: Research was supported by grants from the European Research Council, the Deutsche Forschungsgemeinschaft, the institutional priority program MI-VascAD of the University of Lübeck, and the Marie-Sklodowska-Curie European Union's Horizon 2020 research program.
Spyropoulos et al. (Mon,) studied this question.