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。对正电子发射断层扫描（PET）的研究报告，葡萄糖（RCMRGLC）的区域脑代谢率下降，人类健康衰老。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，因为在rcmrglc纠正了萎缩后不会发生它们。使用PET，我们在纠正萎缩之前和之后测量了RCMRGLC，在“静止”状态（遮盖的眼睛和耳朵塞）的年轻和年龄较大的年轻人中。在萎缩矫正之前，没有统计学上的平均差异，但不存在。因此，与阿尔茨海默氏病不同，健康的人类衰老并不伴随着静息状态脑葡萄糖代谢的降低。 2。大脑突触活动和阿尔茨海默氏病过程中的能耗下降。在批判性综述中，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能量需求，并导致线粒体氧化磷酸化（OXPHOS）的潜在可逆下调。在第二阶段，神经原纤维缠结的异常磷酸化的tau蛋白在神经元细胞质内积聚，直到它们对线粒体在细胞核和突触中的轴突转运所必需的非磷酸化TAU进行。严重的能量耗尽会导致细胞死亡。