Pancreatic thread protein (PTP) is a major exocrine secretory protein that in vitro forms filamentous bundles reminiscent of the paired helical filaments of Alzheimer's disease (AD). We previously described increased PTP immunoreactivity in AD brains and now report high levels in the developing human brain. Using a full-length cloned bovine PTP cDNA and synthetic oligonucleotides corresponding to human PTP cDNA, which is identical to human islet cell regeneration factor, we analyzed the expression of PTP in pancreas and brain. A major 0.9-kb as well as several minor transcripts were identified in human pancreas. In AD brain, the same size transcripts were detected by Northern analysis, primer extension assay, or polymerase chain reaction amplification of cDNAs generated by reverse transcriptase assay. There were significantly higher levels of PTP mRNA in brains with AD compared with aged controls, with increased amounts of 1.2-, 0.6-, and 0.4-kb transcripts by Northern analysis. In situ hybridization localized expression to pyramidal neurons in the cerebral cortex, the same population that contains neurofibrillary tangles and high levels of immunoreactive PTP. These findings suggest that AD is associated with enhanced expression of PTP-related transcripts with intraneuronal accumulation of PTP-like proteins.