D'Andrea Michael R
Johnson & Johnson Pharmaceutical Research & Development, Drug Discovery, Spring House, PA 19477-0776, USA.
Brain Res. 2003 Aug 22;982(1):19-30. doi: 10.1016/s0006-8993(03)02881-6.
The catastrophic loss of cerebral neurons in Alzheimer's disease (AD) is not fully understood. Since serum proteins are known to extravasate into the brain parenchyma in AD due to blood-brain barrier (BBB) dysfunction, this study was designed to explore the possibility that neuronal cell death may be the consequence of the anomalous presence of serum proteins in the brain. As compared to age-matched, non-demented 'control' brain tissues, highly significant increases of immunoglobulins (Igs) were detected in parenchyma, which were associated with vessels in the AD brain tissues. Also, there were dramatic increases of +Ig-neurons in areas with greater parenchymal Ig reactivity. The Ig labeling extended throughout the cell, which showed neurodegenerative apoptotic features that were not observed in -Ig-neurons. Thus, the presence of +Ig-neurons in AD brains implies a critical link between the faulty BBB and neuronal death through an autoimmune mechanism.
阿尔茨海默病（AD）中脑神经元的灾难性损失尚未完全明确。由于已知在AD中，由于血脑屏障（BBB）功能障碍，血清蛋白会渗入脑实质，本研究旨在探讨神经元细胞死亡可能是血清蛋白异常存在于脑内的结果这一可能性。与年龄匹配的非痴呆“对照”脑组织相比，在AD脑组织实质中检测到免疫球蛋白（Igs）显著增加，且这些免疫球蛋白与血管相关。此外，在实质Ig反应性较高的区域，+Ig神经元也显著增加。Ig标记遍布整个细胞，显示出神经退行性凋亡特征，而这些特征在-Ig神经元中未观察到。因此，AD脑中+Ig神经元的存在意味着通过自身免疫机制，存在缺陷的血脑屏障与神经元死亡之间存在关键联系。
