beta-Amyloid precursor protein (beta APP) in human gut with special reference to the enteric nervous system.

The distribution of the beta-amyloid precursor protein (betaAPP) in the human gastrointestinal tract, from esophagus trough rectum, was studied using immunoblotting, as well as combined immunohistochemical and image analysis (optic microdensitometry) techniques. The study was focused on the enteric nervous system. betaAPP was detected by means of a monoclonal antibody (22C11), which recognizes all betaAPP isoforms as well as betaAPP-like proteins. Immunoblotting revealed two main protein bands, one corresponding to full-length betaAPPs (estimated molecular masses of approximately 97-115 kDa); the other corresponded to a protein with estimated molecular masses of 55 kDa. Specific betaAPP immunoreactivity (IR) was found in the submucous and myenteric plexuses localized in the supporting glial cells rather than in neurons. Differences were encountered neither in the localization nor in the intensity of immunostaining among different segments of the gastrointestinal tract. Moreover, no age-dependent changes were found. betaAPP IR was also regularly observed in blood vessels, primarily labelling endothelial cells. Our results provide evidence for the occurrence of betaAPP in human gastrointestinal tract of healthy people in both neuronal and nonneuronal tissues. Whether or not these findings have functional or clinical relevance remains to be clarified in future studies.

Immunoreactivity for beta/A4 protein, but not for its precursor, in human chromaffin cells.

The present study was designed to establish a) whether chromaffin cells of the human adrenal medulla express immunoreactivity for beta-amyloid precursor protein (beta APP) and/or beta-amyloid protein (beta/A4); and b) whether cells expressing one or both of the above-mentioned proteins display immunoreactivity for the low- (gp75) and/or the high-affinity (gp140-trkA) nerve growth factor receptor. To identify chromaffin cells and their supporting cells, chromogranin A, neurofilament proteins, and S-100 protein were studied in parallel. Beta APP and beta/A4 immunoreactivity (IR) was observed primarily labeling two different cell populations, without colocalization: Beta APP IR was found in the adrenal cortical cells, which were mainly localized in the reticulate layer and in the blood vessel walls, whereas beta/A4 IR was observed in the chromaffin cells. Furthermore, supporting cells were also immunoreactive for beta/A4, and sympathetic ganglionic cells were immunoreactive for both beta APP and beta/A4. Interestingly, clusters of cells expressing beta/A4 IR also displayed gp 75 IR and/or gp140-trkA IR. Finally, all chromaffin cells (identified by chromogranin A IR) were immunolabeled for the 200 kDa neurofilament subunit, but not for a phosphorylated epitope of this protein. These results demonstrate the occurrence of beta/A4 IR, but not of beta APP, in the chromaffin cells of the human adrenal gland. The complementary distribution of amyloid-related proteins, and the possible involvement of neurotrophins in beta/A4 metabolism are discussed.

Expression of beta-amyloid precursor protein (APP) in human dorsal root ganglia.

The present study reports the occurrence and localization of beta-amyloid precursor protein (APP) immunoreactivity (IR) in human lumbar dorsal root ganglia of healthy adult subjects (age range 25-43 years). To ascertain that ganglionic cells displayed APP IR, neurofilament (NFP) and S-100 proteins (S100P) were studied in parallel. Immunoblotting revealed four or five major proteins with apparent molecular masses between 100-125 kDa, which corresponded with the different full-length APP isoforms. Moreover, an additional protein of approximately 55 kDa was detected. Selective APP IR was observed restricted to the satellite glial cell cytoplasms whereas neuron cell bodies resulted unlabeled. Moreover, some intraganglionic nerve fibers also displayed APP IR, apparently labelling Schwann cells. No individual differences among subjects were observed neither in the pattern of APP IR distribution, nor in the intensity of APP IR. Although it remains to be demonstrated whether or not human primary sensory neurons express APP, present results strongly suggest that supporting glial cells may be a primary source of APP or any related peptide, at least in adult healthy people. The functional and clinical relevance of these findings, if any, remain to be clarified.