Acta Neuropathol (2011) 122:293–311 305 Fig. 8 Leakages of the cerebrovasculature and cerebral hypoperfu- sion in late-stage TG arcAb mice. Brains of littermates of the TG and arcAb NTG mice used for SEM (Fig. 7) were processed for histological purposes after perfusion with vascular casting resin. Perfusion of the cerebrovasculature with the vascular casting resin showed adequate penetration of arteries and smaller vessels (a, frame). TG littermates showed casting resin leakages similar to those observed with SEM (Fig. 7d) (b, asterisks). Perfusion of the principal source of glucose for the brain [46], it can be appreciated that a decrease in GLUT1 expression will have signiﬁcant outcomes on cerebral glucose uptake. Indeed, cerebral imaging data from human subjects show a clear correlation between GLUT1 expression and blood-to-brain glucose uptake [12]. Our ﬁndings of decreased brain glucose inﬂux and concentration as measured by in vivo microdialysis in TG arcAb mice, are in line with these data. The majority of glucose entering the brain via endothelial GLUT1 is subsequently taken up by astrocytes via astro- cytic GLUT1 [46]. Astrocyte pathology with altered expression of astrocyte-speciﬁc proteins essential for cerebral functioning and metabolism is recognised as a cerebrovasculature with casting resin was, in contrast to the NTG littermates (a, frame), signiﬁcantly impaired in the cortex showing areas lacking ﬂuorescent casting resin and hence resin-negative vessels (b, frame and c). An eventual hypoperfusion due to reduced vascular density was excluded by the ﬁnding of GLUT1-positive endothelium in the non-perfused brain areas (b, frame and d). Scale bar a 150 lm. Hue settings of ﬂuorescence for Ab were altered for more contrast effect explaining the purple colour signiﬁcant factor in AD and subject to intensive research [3, 48]. To understand if a decreased astrocytic GLUT1 expression could also be an underlying factor in the reduced glucose uptake in our microdialysis studies, we cultured astrocytes from the same cohort of arcAb mice ex vivo. We found that its expression was severely affected, starting at mid-stage disease pathology. Astrocytic glucose uptake is a vital step in the cerebral energy apparatus because astrocytes convert glucose into lactate which is used by neurons during neuronal stimulation [14, 29, 38, 43, 44]. Abnormalities in this essential astrocytic contri- bution to neurometabolic coupling have detectable outcomes on cerebral performance and are known to occur 123