Meier-Ruge W, Bertoni-Freddari C, Iwangoff P
Department of Pathology, University Medical School of Basel, Switzerland.
Gerontology. 1994;40(5):246-52. doi: 10.1159/000213592.
The article discusses some aspects demonstrating that a decrease in acetylcholine synthesis in senile dementia of the Alzheimer type (SDAT) is a consequence of the strong decline in glucose turnover in the brain. This becomes obvious by the fact that acetylcoenzyme A, the key substrate of acetylcholine synthesis, is exclusively synthesized in the glycolytic pathway in the brain. This means that a single molecule of glucose synthesizes only two molecules of acetylcoenzyme A but 38 molecules of ATP. This is critically changed if glucose metabolism of the brain decreases in SDAT. beta-Amyloid precursor protein (beta-APP) of chromosome 21 is a regular protein of repair of any cellular membrane in the body. It is integrated into the cellular membranes and split off by proteases in the beta-region. This process is ATP-dependent. If in SDAT ATP synthesis is critically lowered by a decreased glucose turnover, beta-APP cannot be built into the cellular membranes and the beta-APP molecule is not split off in the beta-region either. The consequence is a generation of beta-amyloid from beta-APP fragments, which are progressively accumulated in senile plaques and vascular walls. The missing repair of cellular membranes and synapses in the brain results in nerve cell atrophy and a shrinkage of the brain. It is concluded that the cholinergic deficit, nerve cell atrophy and the amyloid accumulation in the brain are secondary phenomena caused by the 50-70% decline of glucose metabolism in SDAT.
本文讨论了一些方面，表明阿尔茨海默型老年痴呆症（SDAT）中乙酰胆碱合成的减少是大脑中葡萄糖代谢大幅下降的结果。这一点很明显，因为乙酰胆碱合成的关键底物乙酰辅酶A仅在大脑的糖酵解途径中合成。这意味着一个葡萄糖分子只能合成两个乙酰辅酶A分子，但能合成38个ATP分子。如果SDAT中大脑的葡萄糖代谢下降，这种情况就会发生严重变化。21号染色体的β-淀粉样前体蛋白（β-APP）是体内任何细胞膜修复的正常蛋白质。它整合到细胞膜中，并在β区域被蛋白酶切割。这个过程是ATP依赖的。如果在SDAT中，由于葡萄糖代谢下降导致ATP合成严重降低，β-APP就无法整合到细胞膜中，β-APP分子也无法在β区域被切割。结果是由β-APP片段产生β-淀粉样蛋白，这些片段逐渐积聚在老年斑和血管壁中。大脑中细胞膜和突触修复的缺失导致神经细胞萎缩和大脑萎缩。得出的结论是，胆碱能缺陷、神经细胞萎缩和大脑中淀粉样蛋白的积累是SDAT中葡萄糖代谢下降50 - 70%所导致的继发现象。
