Pettegrew J W, Panchalingam K, Moossy J, Martinez J, Rao G, Boller F
Department of Psychiatry, University of Pittsburgh, PA.
Arch Neurol. 1988 Oct;45(10):1093-6. doi: 10.1001/archneur.1988.00520340047010.
Senile plaques (SPs), especially, and neurofibrillary tangles are important pathologic markers for the diagnosis of Alzheimer's disease (AD), but neither is pathognomonic for AD. We hypothesize that elevations in levels of phosphomonoesters, precursors of membrane phospholipids, occur early in the pathogenesis of AD and precede the appearance of SPs. In contrast, elevations in levels of phosphodiesters, breakdown products of phospholipids, reflect degeneration of neural membranes and will correlate with the appearance of SPs. Correlative phosphorus-31 magnetic resonance spectroscopy and morphologic studies conducted to test this hypothesis disclosed that elevations in levels of phosphomonoesters had a negative correlation with the numbers of SPs, and elevations in levels of phosphodiesters had a positive correlation with the numbers of SPs. No correlations were observed for either membrane parameter and neurofibrillary tangles. These findings support our hypothesis and suggest that aberrations in the synthesis of membrane phospholipids are early metabolic events in the pathogenesis of AD.
尤其是老年斑(SPs)和神经原纤维缠结是诊断阿尔茨海默病(AD)的重要病理标志物,但两者都不是AD的特异性标志。我们假设,膜磷脂前体磷酸单酯水平的升高在AD发病机制中出现较早,且早于SPs的出现。相反,磷脂分解产物磷酸二酯水平的升高反映了神经膜的退化,并且将与SPs的出现相关。为检验这一假设而进行的相关磷-31磁共振波谱和形态学研究表明,磷酸单酯水平的升高与SPs的数量呈负相关,磷酸二酯水平的升高与SPs的数量呈正相关。未观察到任何一个膜参数与神经原纤维缠结之间存在相关性。这些发现支持了我们的假设,并表明膜磷脂合成异常是AD发病机制中的早期代谢事件。