We quantified the synaptic density in the outer molecular layer of the hippocampal dentate gyrus. Autopsy material from 9 individuals with Alzheimer disease (AD) were compared to 10 age-matched, postmortem-matched controls without dementia, using standard electron microscopy. Statistical analyses showed a significant change in the density of synapses between controls and AD subjects. There was a significant decline in the width of the entire molecular layer in the AD material. Synaptic density showed a significant correlation with synaptic apposition length in both AD and control groups. As the number of synapses declined, the synaptic apposition length increased. The decline in density of synapses in the AD group might reflect the degree of neuronal loss in the entorhinal cortex. Such a loss in synaptic connectivity could play a key role in memory-related problems associated with AD.