Expression of activating transcription factor-2 (ATF-2), one of the cyclic AMP response element (CRE) binding proteins, in Alzheimer disease and non-neurological brain tissues.

Cyclic AMP response element (CRE) is a specific DNA sequence which mediates transcriptional activation in the response to the cyclic AMP-activated and protein kinase A dependent signaling pathway. We examined the localization of one of the CRE binding proteins which is preferentially expressed in the brain, activating transcription factor-2 (ATF-2), by immunohistochemistry and Southwestern histochemistry, using the brains of neurologically normal and Alzheimer disease (AD) cases. In all brains, the anti-ATF-2 antibody stained white matter microglial cells. In AD, the cytoplasm of some cortical neurons was also positively stained, but no such staining was seen in the neocortex in non-neurological cases staining. However, both the nuclei and cytoplasm of some hippocampal neurons were positive in non-neurological brain tissues. In AD, except for severely damaged areas such as CA1, positive neuronal staining was seen. Southwestern histochemistry gave the same results as immunohistochemistry. These data suggest that the localization of ATF-2 in cortical neurons in AD may reflect early pathological changes characteristic of AD, and that these histochemistrical methods may allow one to differentiate between healthy and mildly damaged neurons.