Calsenilin, a multifunctional Ca2+-binding protein, has been identified as an Alzheimer's disease-associated presenilin interactor. Here, we investigated the histochemical localization of calsenilin and its expression levels in the brains of sporadic Alzheimer's disease. Both messenger RNA and protein expression of calsenilin were observed in neurons of the cerebral cortex and hippocampus of control brains, and more intense staining was in Alzheimer's disease brains. Although calsenilin is primarily expressed in neurons, its immunoreactivity was also detected in reactive astrocytes of the Alzheimer's disease brains. In Alzheimer's disease brains, the caspase-derived fragment of calsenilin was only detected in cytosolic fraction. Our findings suggest that calsenilin overexpression in both neurons and reactive astrocytes may play an important role in apoptosis and in Alzheimer's disease pathology.