Brain Imaging In Human Aging, Alzheimer Disease And Rela

人类衰老、阿尔茨海默病及其相关的脑成像

• 批准号: 6968663
• 负责人: Stanley I. Rapoport
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6968663
• 关键词: Alzheimer' s disease; aging; atrophy; bioimaging /biomedical imaging; brain imaging /visualization /scanning; brain metabolism; glucose metabolism; human subject; magnetic resonance imaging; phosphorylation; positron emission tomography; synapses

1. Studies with positron emission tomography (PET) have reported that regional cerebral metabolic rates for glucose (rCMRglc) decline with healthy aging in humans. In this study, we showed that such declines likely reflect brain atrophy in the elderly, as they do not occur after rCMRglc were corrected for atrophy. With PET, we measured rCMRglc, before and after correcting for atrophy, in young and older healthy young men while in the "resting" state (eyes covered and ears plugged). Statistically significant mean differences were absent after but not before atrophy correction. Thus, healthy human aging, unlike Alzheimer disease, is not accompanied by reduced resting-state brain glucose metabolism. 2. Brain synaptic activity and energy consumption decline in the course of Alzheimer disease. In a critical review, we proposed that in the first stage of disease, changes in synaptic function reduce neuronal energy demand and lead to potentially reversible downregulation of mitochondrial oxidative phosphorylation (OXPHOS). In a second stage, neurofibrillary tangles with abnormally phosphorylated tau protein accumulate within neuronal cytoplasm, until they co-opt the nonphosphorylated tau necessary for axonal transport of mitochondria between the cell nucleus and the synapse. Severe energy depletion leads to cell death.

1.正电子发射断层扫描(PET)研究表明，随着健康年龄的增长，人类大脑局部葡萄糖代谢率(RCMRglc)下降。在这项研究中，我们表明这种下降可能反映了老年人的脑萎缩，因为它们不会在rCMRglc被纠正萎缩后发生。通过正电子发射计算机断层扫描，我们测量了年轻的和年长的健康青年男性在“休息”状态(遮住眼睛和堵住耳朵)前后的rCMRglc。统计学上有意义的平均差异在萎缩矫正后没有，但在萎缩矫正之前没有。因此，与阿尔茨海默病不同，健康的人类衰老并不伴随着静息状态下大脑葡萄糖代谢的降低。 2.阿尔茨海默病病程中脑突触活性和能量消耗下降。在一篇重要的综述中，我们提出在疾病的第一阶段，突触功能的变化减少了神经元的能量需求，并导致潜在的可逆的线粒体氧化磷酸化(OXPHOS)下调。在第二个阶段，神经原纤维与异常磷酸化的tau蛋白在神经元细胞质内积累，直到它们共同参与线粒体在细胞核和突触之间的轴突运输所必需的非磷酸化tau。严重的能量消耗会导致细胞死亡。