In the adult brain we generally observed a nuclear localization for Annexin A7 in neurons whereas astrocytes exhibited both a cytosolic as well as a nuclear staining. However, pyramidal neurons of the isocortex and Purkinje-cells of the cerebellum exhibited a cytosolic stain of intermediate intensity including their neurites and dendrites. We have previously reported the expression of Annexin A7 in human temporal neocortex and hippocampus obtained from neurosurgery for therapy-refractory epilepsy and found the two Annexin A7 isoforms restricted to the cytoplasm and nuclei of astrocytes, whereas neurons lacked any signal [19]. The hippocampal area showed typical signs of Ammon's horn sclerosis, but the adjacent temporal neocortex tissue did not show any histopathological alterations. This data is in discrepancy with our actual observation in the murine brain. To determine if this is due to different methods in immunofluorescence staining or indeed different expression patterns in mouse and human, we repeated the immunofluorescence of human brain. This time we investigated sections from human parietal cortex of autopsy brain. The astroglial expression of Annexin A7 could be confirmed, although not all astrocytes exhibited the nuclear staining. Pyramidal neurons however indicated a distinct staining of Annexin A7 most prominent along their dendrites. The different results obtained for the neurons may be explained by the fact that we previously used frozen tissue sections or that they were derived from patients suffering from temporal lobe epilepsia. On the other hand the actual human brain tissue used was from aged patients and did not correspond to the age of the mice included in this study. In cultured cells after cell damage or apoptosis (unpublished observations) or in cells treated with a Ca2+-ionophore Annexin A7 translocated from the cytoplasm to cellular membranes [19]. We therefore favor the hypothesis that Annexin A7 in the sensitive neurons of the human autopsy brain may have similarly translocated to the cellular membrane. This property of translocation and membrane binding is common to all annexins and commercially available kits for apoptosis detection employ recombinant AnnexinA5. The presence of nuclear Annexin A7 in murine brain was confirmed by controls using sections from the AnxA7-/- mouse and by a biochemical extraction of the protein from the nucleus. Both Annexin A7 isoforms described in brain tissue seemingly are expressed by neurons and astrocytes, which was shown using total cell extracts of cultured neuo-2a, PC-12, and C6 cells. In addition to their expression in brain, both Annexin A7 isoforms have only been described in heart muscle and red blood cells [5-8].