Alzheimer's disease (AD) is characterized by the presence of intracellular neurofibrillary tangles (NFT), extracellular senile plaques (SP), and synaptic loss. The hippocampus is a region that plays an important role in memory and cognitive function, and it is severely affected in AD. The levels of proteins in the hippocampus may provide a better understanding of the pathological changes known. In the present study we used two-dimensional gel electrophoresis and mass spectrometry techniques to determine changes in protein levels in AD and control hippocampus. We identified 18 proteins with altered protein levels that are involved in regulating different cellular functions. Protein levels were found to be significantly decreased for peptidyl prolyl cis/trans-isomerase (Pin 1) (0.6-fold compared to control, p<0.03), dihydropyrimidinase-like protein 2 (DRP-2) (0.74-fold compared to control, p<0.02), phosphoglycerate mutase 1 (PGM1) (0.7-fold compared to control, p<0.01), beta-tubulin (0.34-fold compared to control, p<0.01), and aldolase A (0.87-fold compared to control, p<0.0002), whereas the protein levels were found to be significantly increased for enolase (1.35-fold compared to control, p<0.05), ubiquitin carboxyl terminal hydrolase L-1 (UCH L1) (1.31-fold compared to control, p<0.02), triosephosphate isomerase (TPI) (1.38-fold compared to control, p<0.05), carbonic anhydrase II (CAH-II) (1.24-fold compared to control, p=0.05), heat shock protein 70 (1.14-fold compared to control, p<0.03), fructose bisphosphate aldolase (1.38-fold compared to control, p<0.05), ferritin heavy chain (1.23-fold compared to control, p=0.05), 2',3'-cyclic nucleotide 3' phosphodiestrase (CNPase) (1.12-fold compared to control, p<0.02), peroxiredoxin II (1.39-fold compared to control, p<0.05), and adenylate kinase I (1.19-fold compared to control, p<0.03). We found 2 proteins spots that were identified as glyceraldehyde 3-phosphate dehydrogenase (GAPDH). One of the spots showed a 1.28-fold increase in protein level compared to control (p<0.01), and the other spot showed a similar 1.26-fold increase in protein level compared to control (p<0.04). Thus, proteomics has provided knowledge of the levels of key proteins in AD brain. We discuss the functions regulated by these proteins with respect to AD pathology.