From the Instituto Universitario Fernández-Vega, University of Oviedo, Oviedo, Spain.
Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain.
J Neuropathol Exp Neurol. 2021 Apr 16;80(5):446-456. doi: 10.1093/jnen/nlab028.
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.
乙酰肝素硫酸的糖链似乎参与了阿尔茨海默病（AD）发病机制的多个方面。其结构的复杂性归因于不同同工酶的表达。我们研究了 AD 大脑中乙酰肝素硫酸链生物合成的差异转录，分析了具有不同 AD 病理程度的患者的不同脑区。使用来自轻度、中度或重度 AD 患者以及健康个体的杏仁核、前海马体、后海马体、屏状核、距状裂、苍白球和小脑样本，通过 RT-PCR 进行了转录组研究。通过免疫组织化学检测了某些乙酰肝素硫酸表位。在 AD 患者的不同脑区中，跨乙酰肝素硫酸合成所有阶段的某些基因的转录发生了改变。在中度 AD 患者中，改变的数量多于轻度 AD 患者。在重度患者中，与早期生物合成相关的基因的改变较少，而与晚期相关的基因表达增加。这些改变与进行性脑萎缩相关，尽管在小脑更常见。免疫组织化学检测到的一些乙酰肝素硫酸表位与之前的研究一致。总之，乙酰肝素硫酸生物合成基因的转录改变取决于脑区和 AD 病理的程度。
