Department of Ophthalmology, Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California 90089-0228, USA.
J Neuroophthalmol. 2011 Jun;31(2):139-46. doi: 10.1097/WNO.0b013e31821b602c.
Alzheimer disease (AD) is associated with optic nerve degeneration, yet the underlying pathophysiology of this disease and the optic nerve disorder remain poorly understood. Low-density lipoprotein receptor-related protein (LRP) is implicated in the pathogenesis of AD by mediating the transport of amyloid-β (Aβ) out of the brain into the systemic circulation. As a key player in the reaction to central nervous system injury, astrocytes associate with LRP in AD. This study investigates the role of LRP and astrocytes in the pathogenesis of AD optic neuropathy.
To investigate the role of LRP and astrocytes in the pathogenesis of AD optic neuropathy, we conducted immunohistochemical studies on postmortem optic nerves in AD patients (n = 11) and age-matched controls (n = 10) to examine the presence of LRP. Quantitative analyses using imaging software were used to document the extent of LRP in neural tissues. Axonal integrity was assessed by performing immunohistochemistry on the subjects' optic nerves with an antibody to neurofilament (NF) protein. Double-immunofluorescence labeling was performed to investigate whether LRP colocalized with astrocytes, expressing glial fibrillary acidic protein.
LRP expression was decreased in AD optic nerves compared to that in controls (P < 0.001). LRP immunoreactivity was observed in the microvasculature and perivascularly in close proximity to the astrocytic processes. Colocalization of LRP in the astrocytes of optic nerves was also demonstrated. The presence of optic neuropathy was confirmed in the AD optic nerves by demonstrating greatly reduced immunostaining for NF protein as compared to controls.
The reduction of LRP in the AD degenerative optic nerves supports the hypothesis that LRP may play a role in the pathophysiology of AD optic neuropathy.
阿尔茨海默病（AD）与视神经变性有关，但这种疾病的潜在病理生理学和视神经障碍仍知之甚少。载脂蛋白-β（Aβ）通过介导其从大脑运出到全身循环，低密度脂蛋白受体相关蛋白（LRP）被认为与 AD 的发病机制有关。星形胶质细胞在 AD 中与 LRP 相关，是中枢神经系统损伤反应的关键参与者。本研究旨在探讨 LRP 和星形胶质细胞在 AD 视神经病变发病机制中的作用。
为了研究 LRP 和星形胶质细胞在 AD 视神经病变发病机制中的作用，我们对 AD 患者（n=11）和年龄匹配的对照组（n=10）的死后视神经进行了免疫组织化学研究，以检查 LRP 的存在。使用成像软件进行定量分析，记录神经组织中 LRP 的程度。通过对研究对象的视神经进行神经丝蛋白（NF）蛋白免疫组织化学染色，评估轴突完整性。进行双免疫荧光标记以研究 LRP 是否与表达神经胶质纤维酸性蛋白的星形胶质细胞共定位。
与对照组相比，AD 视神经中的 LRP 表达减少（P<0.001）。LRP 免疫反应性在微血管中观察到，并在星形胶质细胞突起附近的血管周围接近。还证明了视神经中 LRP 与星形胶质细胞的共定位。与对照组相比，AD 视神经中 NF 蛋白免疫染色显著减少，证实了存在视神经病变。
AD 退行性视神经中 LRP 的减少支持了 LRP 可能在 AD 视神经病变的病理生理学中发挥作用的假设。
