Wide distribution of CREM immunoreactivity in adult and fetal human brain, with an increased expression in dentate gyrus neurons of Alzheimer's as compared to normal aging brains.

Human cyclic AMP response modulator proteins (CREMs) are encoded by the CREM gene, which generates 30 or more different CREM protein isoforms. They are members of the leucine zipper protein superfamily of nuclear transcription factors. CREM proteins are known to be implicated in a plethora of important cellular processes within the CNS. Amazingly, little is known about their cellular and regional distribution in the brain, however. Therefore, we studied by means of immunohistochemistry and Western blotting the expression patterns of CREM in developing and adult human brain, as well as in brains of Alzheimer's disease patients. CREM immunoreactivity was found to be widely but unevenly distributed in the adult human brain. Its localization was confined to neurons. In immature human brains, CREM multiple neuroblasts and radial glia cells expressed CREM. In Alzheimer's brain, we found an increased cellular expression of CREM in dentate gyrus neurons as compared to controls. We discuss our results with regard to the putative roles of CREM in brain development and in cognition.