Grammas P, Yamada M, Zlokovic B
Department of Pathology and the Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, 975 NE 10th Street, Biomedical Research Center, Oklahoma City, OK 73104, USA.
J Alzheimers Dis. 2002 Jun;4(3):217-23. doi: 10.3233/jad-2002-4311.
Neuronal cell death is the primary underlying pathogenic lesion in Alzheimer's disease (AD). Despite intense research efforts, the mechanisms that contribute to neuronal cell death have not been clarified. In this debate we address the question, Is AD a vascular or metabolic disorder? Here we defend the hypothesis that the cerebromicrovasculature is a key player in the pathogenesis of AD. Evidence is presented that vascular amyloid beta (Abeta) is more closely associated with tau pathology than the distribution of diffuse or neuritic plaque Abeta. Furthermore, brain endothelial cells are identified as important regulators of the neuronal microenvironment, including Abeta levels. Finally, evidence is presented that brain endothelial cells undergo cellular and biochemical changes in AD and that the release of neurotoxic factors from these dysfunctional cells contributes to the neuronal cell loss characteristic of AD.
神经元细胞死亡是阿尔茨海默病（AD）的主要潜在致病损伤。尽管进行了大量深入研究，但导致神经元细胞死亡的机制仍未阐明。在这场辩论中，我们探讨一个问题：AD是血管性疾病还是代谢性疾病？在此，我们捍卫这样一种假说，即脑微血管系统在AD发病机制中起关键作用。有证据表明，血管淀粉样β蛋白（Aβ）与tau病理的关联比弥漫性或神经炎斑块Aβ的分布更为密切。此外，脑内皮细胞被确定为神经元微环境（包括Aβ水平）的重要调节因子。最后，有证据表明，AD患者的脑内皮细胞会发生细胞和生化变化，这些功能失调细胞释放的神经毒性因子导致了AD特有的神经元细胞丢失。
