Alterations in the Expression of the Genes Responsible for the Synthesis of Heparan Sulfate in Brains With Alzheimer Disease

Abstract

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.

Keywords: Alzheimer disease; Glycosaminoglycan; Heparan sulfate; Heparan sulfate sulfotransferase.