Loss of synapses has been shown to correlate with the severity of dementia in Alzheimer's disease (AD). Intracellular neurofibrillary tangles (NFTs) have also been shown to correlate to the severity of AD dementia. We have been investigating the influence of NFTs on mRNAs related to neuronal plasticity and synaptic function. We recently reported a decrease in message for the plasticity marker, GAP-43, in AD cases with high tangle densities. The study did not permit us to determine if: a) the decrease in GAP-43 message was specific to the NFT-bearing neurons, b) a general decrease in GAP-43 message was occurring in all surviving neurons, or c) the decrease in GAP-43 message was due to a loss of neurons. It is unlikely a loss of neurons could explain the sixfold GAP-43 message loss we reported, because only a 19% excess decrease in density of hippocampal neurons occurs in AD cases with high tangle densities. Consequently, the study reported here was undertaken to determine if a general decrease in GAP-43 message was occurring in all surviving AD neurons or if the decrease in GAP-43 message was specific to NFT-bearing neurons. We combined immunocytochemistry for neurofibrillary tangles with in situ hybridization for GAP-43 message. We report here preliminary evidence indicating a decrease in GAP-43 message in NFT-bearing neurons compared to adjacent nontangle bearing neurons in parahippocampal cortex of AD patients.