Kowall N W, Beal M F, Busciglio J, Duffy L K, Yankner B A
Department of Neurology, Massachusetts General Hospital, Boston 02114.
Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7247-51. doi: 10.1073/pnas.88.16.7247.
Deposition of the beta-amyloid protein in senile plaques is a pathologic hallmark of Alzheimer disease (AD). Focal deposition of beta amyloid in the adult rat cerebral cortex caused profound neurodegenerative changes, including neuronal loss and degenerating neurons and neurites. Chronic induction of the Alz-50 antigen appeared in neurons around focal cortical deposits of beta amyloid. Immunoblot analysis showed that beta amyloid induced Alz-50-immunoreactive proteins in rat cerebral cortex that were very similar to the proteins induced in human cerebral cortex from patients with AD. The neuropeptide substance P prevented beta-amyloid-induced neuronal loss and expression of Alz-50 proteins when coadministered into the cerebral cortex. Systemic administration of substance P also provided protection against the effects of intracerebral beta amyloid. Thus, beta amyloid is a potent neurotoxin in the adult brain in vivo, and its effects can be blocked by substance P.
β-淀粉样蛋白在老年斑中的沉积是阿尔茨海默病（AD）的病理标志。β-淀粉样蛋白在成年大鼠大脑皮层的局灶性沉积引起了严重的神经退行性变化，包括神经元丢失以及神经元和神经突的退变。在β-淀粉样蛋白局灶性皮层沉积物周围的神经元中出现了Alz-50抗原的慢性诱导。免疫印迹分析表明，β-淀粉样蛋白在大鼠大脑皮层中诱导出Alz-50免疫反应性蛋白，这些蛋白与AD患者大脑皮层中诱导出的蛋白非常相似。当与β-淀粉样蛋白共同注入大脑皮层时，神经肽P物质可防止β-淀粉样蛋白诱导的神经元丢失和Alz-50蛋白的表达。全身性给予P物质也能保护大脑免受脑内β-淀粉样蛋白的影响。因此，β-淀粉样蛋白在成年动物大脑中是一种有效的神经毒素，其作用可被P物质阻断。
