Rozeboom Annemieke, Broekaart Diede W M, Anink Jasper J, Boonkamp Lynn, Idema Sander, Teunissen Charlotte E, Aronica Eleonora, Gorter Jan A, van Vliet Erwin A
Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam UMC, University of Amsterdam, Department of (Neuro) Pathology, Amsterdam Neuroscience, Meibergdreef 9, Amsterdam, the Netherlands.
Amsterdam UMC, University of Amsterdam, Department of (Neuro) Pathology, Amsterdam Neuroscience, Meibergdreef 9, Amsterdam, the Netherlands.
Exp Neurol. 2025 Apr;386:115149. doi: 10.1016/j.expneurol.2025.115149. Epub 2025 Jan 20.
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.
低密度脂蛋白受体相关蛋白1（LRP1）在毛细血管中的表达降低与阿尔茨海默病（AD）患者脑内淀粉样β蛋白（Aβ）积累增加有关。在颞叶癫痫（TLE）患者（部分患者）中也观察到了Aβ积累，提示癫痫与AD之间可能存在联系。本研究检测人及大鼠癫痫源性脑组织中细胞LRP1的表达，以探讨LRP1在癫痫中的作用。采用免疫组化法分析癫痫持续状态（SE，n = 12）、TLE（n = 12）、尸检对照（n = 20）及AD（n = 10）患者海马切片中LRP1的表达及定位。比较TLE、AD及对照组织中可溶性Aβ水平及沉积情况。还在TLE的电刺激SE后大鼠模型中研究了LRP1的表达。在人和大鼠脑组织（SE和TLE）中均发现毛细血管LRP1表达降低。在CA1神经元（仅在人TLE中）和神经胶质细胞（SE和TLE）中检测到较高的LRP1表达。12例TLE患者中仅1例观察到Aβ沉积，可溶性Aβ水平未显著升高。相比之下，AD患者毛细血管LRP1表达降低，伴有Aβ斑块形成且可溶性Aβ40/42水平升高。成人和大鼠TLE脑毛细血管中LRP1表达的显著降低与明显的Aβ积累无明显关联，这意味着血管中除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病理改变可能不如一些研究所表明的那么突出。
