de la Torre J C
University of New Mexico, Division of Neurosurgery, Albuquerque 87131, USA.
Ann N Y Acad Sci. 1997 Sep 26;826:75-91. doi: 10.1111/j.1749-6632.1997.tb48462.x.
The cause of sporadic Alzheimer's disease (AD) remains a mystery. Mounting clinical and experimental data, however, suggest that a cerebral hemodynamic role may affect neuronoglial metabolism. Light and electron microscopy have consistently revealed that the microvasculature in AD brains contains structurally deformed capillaries which create a distorted intraluminal conduit for blood flow. The cerebral capillary distortions can create "disturbed" rather than "laminar" blood flow. Chronically disturbed capillary blood flow will impair normal delivery of essential nutrients to brain neurons as well as impede catabolic outflow of CNS waste products. This condition will negatively affect cerebral metabolism, primarily because of impaired glucose delivery to neurons. Impaired glucose delivery to AD brain results in a patho-chemical cascade that will impair the Na+, K(+)-ATPase ion pump and affect the syntheses of ATP, acetylcholine, and other neurotransmitters. The outcome of this metabolic dysfunction can promote neurofibrillary tangle and senile plaque formation in AD brain.
散发性阿尔茨海默病(AD)的病因仍是个谜。然而,越来越多的临床和实验数据表明,脑血流动力学作用可能会影响神经胶质细胞代谢。光学显微镜和电子显微镜一直显示,AD大脑中的微血管含有结构变形的毛细血管,这些毛细血管为血流形成了扭曲的管腔内通道。脑毛细血管扭曲会导致血流“紊乱”而非“层流”。长期紊乱的毛细血管血流会损害向脑神经元正常输送必需营养物质的过程,同时也会阻碍中枢神经系统代谢废物的分解流出。这种情况会对脑代谢产生负面影响,主要是因为向神经元输送葡萄糖的过程受损。向AD大脑输送葡萄糖受损会引发病理化学级联反应,这将损害钠钾ATP酶离子泵,并影响ATP、乙酰胆碱和其他神经递质的合成。这种代谢功能障碍的结果会促进AD大脑中神经原纤维缠结和老年斑的形成。