The saccharide chains of heparan sulfate appear to be involved in several aspects Alzheimer disease (AD) pathogenesis. Their structural complexity is due to the expression of different isoenzymes. We studied the differential transcription of heparan sulfate chain biosynthesis in AD brains, analyzing different brain regions in patients with different extents of AD pathology. The transcriptomic study was performed by RT-PCR using samples of amygdala, anterior hippocampus, posterior hippocampus, claustrum, calcarine fissure, globus pallidus and cerebellum from patients with mild, moderate, or severe AD, as well as healthy individuals. Certain heparan sulfate epitopes were also detected by immunohistochemistry. Several genes, across all stages of heparan sulfate synthesis, showed altered transcription in different brain regions of AD patients. The numbers of alterations were greater in in moderate versus mild AD patients. In severe patients, there were fewer alterations in genes related to early stages of biosynthesis, and overexpression of genes involved in late stages. The alterations correlated with progressive brain atrophy, although alterations were more common in the cerebellum. Detection of some heparan sulfate epitopes by immunohistochemistry was consistent with previous studies. In conclusion, transcriptional alterations in the biosynthetic genes of heparan sulfate depend on the brain region and the degree of AD pathology.

Small leucine-rich proteoglycans (SLRPs) regulate different processes and undergo significant alterations in various diseases. Colon carcinomas (CCs) are heterogeneous pathologies with important clinical and molecular differences depending on their location, which makes it interesting to analyze the alterations in SLRPs in right- and left-sided tumors (RS- and LSCCs). SLRP transcription levels were studied in 32 CCs using qPCR compared to healthy colon mucosae samples from the same patients, 20 of them from LSCCs and the remaining 12 from RSCCs. Protein expression of genes with significant differences in their transcriptions was analyzed by immunohistochemistry. The alterations observed were related to survival data. The arrangement of transcription of SLRPs was quite similar in ascending and descending colon, but RS- and LSCCs displayed different patterns of alteration, with a greater number of deregulations occurring in the latter. The analysis of protein expression also indicated changes in the location of these molecules, largely moving to the cell interior. While podocan underexpression showed a trend toward better outcomes, no differences were observed in terms of overall survival. In vitro studies using the HT29 tumor cell line suggest that deregulation of SLRPs could affect cell proliferation. SLRPs constitute new differential markers of RS- and LSCCs, showing differences dependent on the anatomical location of the tumor.