PDF(Pubmed)
Abstract：
Alzheimer\'s disease (AD) is a debilitating neurodegenerative disease characterized by the accumulation of extracellular amyloid-β peptides (Aβ) within the cerebral parenchyma and vasculature, which is known as cerebral amyloid angiopathy (CAA). This study utilized confocal imaging to investigate heparan sulfate (HS) expression within the cerebrovasculature and its associations with Aβ, gender, and ApoE4 genotype in AD. Our investigation revealed elevated levels of HS in the cerebrovasculature of AD patients with severe CAA. Additionally, these patients exhibited higher HS colocalization with Aβ in the cerebrovasculature, including both endothelial and vascular smooth muscle cell compartments. Intriguingly, a reversal in the polarized expression of HS within the cerebrovasculature was detected in AD patients with severe CAA. Furthermore, male patients exhibited lower levels of both parenchymal and cerebrovascular HS. Additionally, ApoE4 carriers displayed heightened cerebrovascular Aβ expression and a tendency of elevated cerebrovascular HS levels in AD patients with severe CAA. Overall, these findings reveal potential intricate interplay between HS, Aβ, ApoE, and vascular pathology in AD, thereby underscoring the potential roles of cerebrovascular HS in CAA development and AD pathology. Further study of the underlying mechanisms may present novel therapeutic avenues for AD treatment.
摘要：
阿尔茨海默病（AD）是一种使人衰弱的神经退行性疾病，其特征是脑实质和脉管系统内胞外淀粉样β肽（Aβ）的积累，这被称为脑淀粉样血管病（CAA）。本研究利用共聚焦成像来研究硫酸乙酰肝素（HS）在脑血管系统中的表达及其与Aβ，性别,和ApoE4基因型在AD。我们的调查显示，患有严重CAA的AD患者的脑血管中HS水平升高。此外,这些患者在脑血管系统中表现出更高的HS与Aβ的共定位，包括内皮和血管平滑肌细胞区室。有趣的是，在患有严重CAA的AD患者中，检测到脑血管系统中HS的极化表达逆转。此外，男性患者的实质和脑血管HS水平均较低。此外,ApoE4携带者在患有严重CAA的AD患者中显示出脑血管Aβ表达升高和脑血管HS水平升高的趋势。总的来说,这些发现揭示了HS之间潜在的复杂相互作用，Aβ,ApoE,和AD的血管病理学，从而强调脑血管HS在CAA发展和AD病理中的潜在作用。对潜在机制的进一步研究可能为AD治疗提供新的治疗途径。
