低密度脂蛋白受体相关蛋白1的细胞表达和β淀粉样蛋白沉积在人和大鼠致痫脑。

IF 4.6 2区医学 Q1 NEUROSCIENCES

Experimental Neurology Pub Date : 2025-01-20 DOI:10.1016/j.expneurol.2025.115149

Annemieke Rozeboom , Diede W.M. Broekaart , Jasper J. Anink , Lynn Boonkamp , Sander Idema , Charlotte E. Teunissen , Eleonora Aronica , Jan A. Gorter , Erwin A. van Vliet

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引用次数: 0

摘要

低密度脂蛋白受体相关蛋白1 （LRP1）的毛细血管表达减少与阿尔茨海默病（AD）中脑淀粉样蛋白β (Aβ)积累增加有关。在部分颞叶癫痫（TLE）患者中也观察到a β积累，提示癫痫和AD之间存在潜在联系。本研究通过检测人类和大鼠致痫脑组织中LRP1的细胞表达，探讨LRP1在癫痫中的作用。应用免疫组织化学方法分析LRP1在癫痫持续状态（SE, n = 12）、TLE （n = 12）、尸检对照（n = 20）和AD （n = 10）患者海马切片中的表达和定位。比较TLE、AD和对照组织中可溶性Aβ水平和沉积。LRP1的表达也在电性se后大鼠TLE模型中进行了研究。人和大鼠脑组织（SE和TLE）毛细血管LRP1表达均降低。在CA1神经元（仅在人TLE中）和胶质细胞（SE和TLE）中检测到较高的LRP1表达。12例TLE患者中仅有1例出现Aβ沉积，可溶性Aβ水平无显著升高。相比之下，AD患者毛细血管LRP1表达降低，伴有Aβ斑块，可溶性Aβ40/42水平升高。成人和大鼠TLE脑毛细血管中LRP1表达的显著降低与显著的Aβ积累没有明显关联，这意味着血管中LRP1之外的其他淀粉样蛋白清除机制可能在起作用。这也支持了先前的研究结果，即成人TLE中的Aβ病理可能不像一些研究表明的那样突出。

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Cellular expression of low-density lipoprotein receptor-related protein 1 and amyloid beta deposition in human and rat epileptogenic brain

Decreased capillary expression of low-density lipoprotein receptor-related protein 1 (LRP1) has been linked to increased brain amyloid beta (Aβ) accumulation in Alzheimer's disease (AD). Aβ accumulation has also been observed in (a subset of) temporal lobe epilepsy (TLE) patients, suggesting a potential link between epilepsy and AD. This study examines cellular LRP1 expression in human and rat epileptogenic brain tissue to explore LRP1's role in epilepsy.

LRP1 expression and localization were analyzed in hippocampal sections from patients with status epilepticus (SE, n = 12), TLE (n = 12), autopsy controls (n = 20), and AD (n = 10) using immunohistochemistry. Soluble Aβ levels and deposits were compared across TLE, AD, and control tissues. LRP1 expression was also studied in an electrical post-SE rat model of TLE.

Decreased capillary LRP1 expression was found in both human and rat brain tissue (SE and TLE). Higher LRP1 expression was detected in CA1 neurons (only in human TLE) and glial cells (SE and TLE). Aβ deposits were observed in only one out of 12 TLE patients, and soluble Aβ levels were not significantly elevated. In contrast, AD patients showed decreased capillary LRP1 expression accompanied by Aβ plaques and increased soluble Aβ40/42 levels.

The significant reduction in LRP1 expression in brain capillaries in both adult human and rat TLE was not clearly associated with notable Aβ accumulation implying that alternative amyloid clearance mechanisms beyond LRP1 in blood vessels might be at play. It also supports previous findings indicating that Aβ pathology may be less prominent in adult TLE than some studies suggest.

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来源期刊

Experimental Neurology 医学-神经科学

CiteScore

10.10

自引率

3.80%

发文量

258

审稿时长

42 days

期刊介绍： Experimental Neurology, a Journal of Neuroscience Research, publishes original research in neuroscience with a particular emphasis on novel findings in neural development, regeneration, plasticity and transplantation. The journal has focused on research concerning basic mechanisms underlying neurological disorders.