Accumulating evidence suggests that a disruption of zinc (Zn) homeostasis may play a role in the pathogenesis of Alzheimer's disease. Although several Zn transporter proteins responsible for the regulation of Zn balance are present in the brain, there has been little study of these proteins in Alzheimer's disease. To determine if alterations of Zn transporter proteins exist, levels of Zn transporter-4, which functions to remove Zn from the cytoplasm to endosomal/lysosomal compartments, and Zn transporter-6, which allocates cytoplasmic Zn to the trans-Golgi network, were measured in the hippocampus/parahippocampal gyrus, superior and middle temporal gyrus, and cerebellum of subjects with mild cognitive impairment, early Alzheimer's disease, late stage Alzheimer's disease, and age-matched controls using Western blot analysis and protein specific antibodies. Our results show that Zn transporter-4 and Zn transporter-6 are significantly (P<0.05) increased in hippocampus/parahippocampal gyrus of early Alzheimer's disease and Alzheimer's disease subjects. Zn transporter-6 is also increased (P<0.1) in the superior and middle temporal gyrus of Alzheimer's disease brain.