306 Acta Neuropathol (2011) 122:293–311 Fig. 9 In vivo leakages of the cerebrovasculature in late-stage TG arcAb mice are not paralleled by haemorrhages, suggesting small BBB disruptions. a Intraperitoneal injection of late-stage TG mice and their arcAb NTG littermates with Trypan Blue showed extrav- asations of Trypan blue mainly around small vessels in the TG animals (asterisks). Bigger arterioles (a, plus sign) and arteries (a, arrow) were found to accumulate Trypan Blue within the vessel wall. Both small vessel extravasation and arterial accumulation of Trypan Blue within the vessel wall was only seen for vessels affected in AD [3, 50]. The impaired lactate release we observed upon in vivo neuronal stimulation during microdialysis in TG arcAb mice, was conﬁrmed by a decreased astrocytic MCT1 expression and lactate release deﬁciency ex vivo. The reciprocal character of the expression proﬁles of MCT1 and GLUT1 as shown by Maurer and colleagues [33] makes plausible that the decreased astrocytic MCT1 protein levels could be related to lower astrocytic GLUT1. 123 by CAA. Scale bar a 150 lm. Hue settings of ﬂuorescence for Trypan Blue were altered for more contrast effect explaining the blue colour. (b) Thioﬂavin S staining (green-yellow) combined with Prussian Blue staining (dark blue, asterisk) showed CAA-related presence of haemorrhages. Scale bar b 30 lm. The number of haemorrhages was signiﬁcantly lower than Trypan Blue extravasations (c) and not chronically paralleled by vascular casting resin protrusions (d). Scale bar d 150 lm Astrocytic GLUT1 and MCT1 are mainly expressed on astrocyte endfeet which are crucial for neurovascular coupling [1, 3, 65]. Impaired neurovascular coupling is common in neurodegenerative disorders including AD and AD mouse models with astrocyte endfeet retraction and swelling compromising the cross-talk between astrocytes, blood vessels and neurons and decreased cerebral metab- olism as histological and functional hallmarks [3, 37, 61].