298 Acta Neuropathol (2011) 122:293–311 Fig. 1 Endothelial GLUT1 but not neuronal GLUT3 protein expres- sion and basal glucose levels are decreased in the TG arcAb mouse brain from mid-stage pathology onwards. a Immunohistochemical staining of a representative cortical brain section showing GLUT1 protein expression on CAA and non-CAA blood vessels in a mid- stage TG arcAb mouse. Reduced GLUT1 immuno-staining (arrow) on a CAA-vessel (stained with antibody 6E10, arrow) can be seen. However, CD31—a marker for endothelial cells—was not affected and eventual impaired staining for GLUT1 due to antigen-masking by CAA (arrow) could be ruled out. b Immunohistochemical staining of a representative cortical brain section of a mid-stage arcAb mouse shows that in areas with dense presence of diffuse Ab plaques also non-CAA vessels had reduced GLUT1 protein expression, whereas during continuous microdialysis sampling (Fig. 2c, sample 5, single arrow). Fifteen 5-min interval microdialysis samples were collected (samples 5–19), followed by four 30-min samples (samples 20–23). Whereas in the microdialysate of the NTG animals ﬁrst a clear fall in glucose was measured in the 5-min interval microdialysate sample collected during and directly after injection of glucose (sample 5, single arrow) and then a steep rise to a new glucose concentration plateau was established, no such change in the glucose concentration proﬁle was seen in the TG arcAb mice. Contrary to these ﬁndings, retrodialysis of 120 mM potassium chloride (KCl) to stimulate neuronal activity combined with intraperitoneal 123 CD31 staining was preserved on these vessels (arrows). CD31 was found to be continuously expressed on the whole length of the vessels in contrast to GLUT1 which showed interruptions in the staining pattern (outlined section). c Statistical analysis of CD31 and GLUT1 expression on CAA-vessels in mid-stage arcAb mice. Immunostain- ing for GLUT1 was signiﬁcantly lower on these CAA-vessels as compared to the CD31 staining. Student’s t test, p = 0.0004 (n = 35 CAA vessels). d Western blots of hippocampus and cortex of mid- stage TG arcAb mice and NTG littermates demonstrating that the endothelial GLUT1 protein expression (55 kDa) was reduced in TG animals as compared to their NTG littermates. No differences were found in the levels of the neuronal GLUT3 protein. Scale bar a 100 lm; b 300 lm administration of 250 mg glucose/kg body weight (Fig. 2c, sample 24, double arrows) led to a sharp fall and then steep rise in glucose concentration in the microdialysate of both NTG and TG mice. Impaired lactate release upon neuronal stimulation and reduced expression of the astrocytic lactate transporter MCT1 in mid-stage arcAb mice To analyse the consequences of impaired glucose con- centration proﬁles on neuronal functioning, the release of lactate during neuronal stimulation was assessed. Lactate