Department of Nuclear Medicine and Center for PET, Austin Health, 145 Studley Road, Heidelberg, Victoria 3084, Australia.
Ann Neurol. 2010 Mar;67(3):317-24. doi: 10.1002/ana.21955.
Elucidating the role of aggregated beta-amyloid in relation to gray matter atrophy is crucial to the understanding of the pathological mechanisms of Alzheimer disease and for the development of therapeutic trials. The present study aims to assess this relationship.
Brain magnetic resonance imaging and [(11)C]Pittsburgh compound B (PiB)-positron emission tomography scans were obtained from 94 healthy elderly subjects (49 with subjective cognitive impairment), 34 patients with mild cognitive impairment, and 35 patients with Alzheimer disease. The correlations between global and regional neocortical PiB retention and atrophy were analyzed in each clinical group.
Global and regional atrophy were strongly related to beta-amyloid load in participants with subjective cognitive impairment but not in patients with mild cognitive impairment or Alzheimer disease. Global neocortical beta-amyloid deposition correlated to atrophy in a large brain network including the hippocampus, medial frontal and parietal areas, and lateral temporoparietal cortex, whereas regional beta-amyloid load was related to local atrophy in the areas of highest beta-amyloid load only, that is, medial orbitofrontal and anterior and posterior cingulate/precuneus areas.
There is a strong relationship between beta-amyloid deposition and atrophy very early in the disease process. As the disease progresses to mild cognitive impairment and Alzheimer disease clinical stages, pathological events other than, and probably downstream from, aggregated beta-amyloid deposition might be responsible for the ongoing atrophic process. These findings suggest that antiamyloid therapy should be administered very early in the disease evolution to minimize synaptic and neuronal loss.
阐明聚集β-淀粉样蛋白与灰质萎缩之间的关系，对于理解阿尔茨海默病的病理机制以及开发治疗试验至关重要。本研究旨在评估这种关系。
对 94 名健康老年人（49 名有主观认知障碍）、34 名轻度认知障碍患者和 35 名阿尔茨海默病患者进行了脑磁共振成像和 [(11)C]匹兹堡化合物 B（PiB）-正电子发射断层扫描。分析了每个临床组中全局和区域新皮质 PiB 保留与萎缩之间的相关性。
在有主观认知障碍的参与者中，全局和区域萎缩与β-淀粉样蛋白负荷强烈相关，但在轻度认知障碍或阿尔茨海默病患者中则不相关。全球新皮质β-淀粉样蛋白沉积与包括海马、内侧额顶区和外侧颞顶叶皮层在内的大脑网络的萎缩相关，而区域β-淀粉样蛋白负荷仅与β-淀粉样蛋白负荷最高的区域的局部萎缩相关，即内侧眶额和前后扣带回/楔前叶区域。
在疾病过程的早期，β-淀粉样蛋白沉积与萎缩之间存在很强的关系。随着疾病进展到轻度认知障碍和阿尔茨海默病的临床阶段，除了聚集β-淀粉样蛋白沉积之外，可能还有其他的病理事件，而且可能是其下游事件，导致了持续的萎缩过程。这些发现表明，抗淀粉样蛋白治疗应该在疾病演变的早期进行，以最大程度地减少突触和神经元的丧失。
