Department of Radiology and Biomedical Imaging, University of California - San Francisco, San Francisco, CA, USA.
Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA.
Brain. 2017 May 1;140(5):1499-1512. doi: 10.1093/brain/awx046.
See Vandenberghe and Schaeverbeke (doi:10.1093/awx065) for a scientific commentary on this article. A long-term goal of our field is to determine the sequence of pathological events, which ultimately lead to cognitive decline and dementia. In this study, we first assessed the patterns of brain tau tangle accumulation (measured with the positron emission tomography tracer 18F-AV-1451) associated with well-established Alzheimer's disease factors in a cohort including cognitively healthy elderly individuals and individuals at early symptomatic stages of Alzheimer's disease. We then explored highly associated patterns of greater 18F-AV-1451 binding and increased annualized change in cortical amyloid-β plaques measured as florbetapir positron emission tomography binding antecedent to 18F-AV-1451 positron emission tomography scans, and to what extent these multimodal pattern associations explained the variance in cognitive performance and clinical outcome measures, independently and jointly. We found that: (i) 18F-AV-1451 positron emission tomography retention was differentially associated with age, and cross-sectional florbetapir positron emission tomography retention, but not with years of education, gender, or APOE genotype; (ii) increased annualized change in florbetapir retention, antecedent to 18F-AV-1451 positron emission tomography scans, in the parieto-temporal and precuneus brain regions was associated with greater 18F-AV-1451 PET retention most prominently in the inferior temporal and inferior parietal regions in the full cohort, with florbetapir positive/negative-associated variability; and (iii) this 18F-AV-1451 positron emission tomography retention pattern significantly explained the variance in cognitive performance and clinical outcome measures, independent of the associated antecedent increased annualized change in florbetapir positron emission tomography retention. These findings are in agreement with the pathology literature, which suggests that tau tangles but not amyloid-β plaques correlate with cognition and clinical symptoms. Furthermore, non-local associations linking increased amyloid-β accumulation rates with increased tau deposition are of great interest and support the idea that the amyloid-β pathology might have remote effects in disease pathology spread potentially via the brain's intrinsic connectivity networks.
请参阅 Vandenberghe 和 Schaeverbeke（doi:10.1093/awx065）的相关科学评论。我们领域的长期目标是确定导致认知能力下降和痴呆的病理事件序列。在这项研究中，我们首先评估了与认知健康的老年人和处于阿尔茨海默病早期症状阶段的个体中已确立的阿尔茨海默病因素相关的脑 tau 缠结（用正电子发射断层扫描示踪剂 18F-AV-1451 测量）的积累模式。然后，我们探索了与皮质淀粉样β斑块的 18F-AV-1451 结合增加以及 florbetapir 正电子发射断层扫描结合增加的高度相关模式，这些淀粉样β斑块是在 18F-AV-1451 正电子发射断层扫描之前进行的，以及这些多模式模式关联在多大程度上独立和共同解释了认知表现和临床结果测量的变异性。我们发现：（i）18F-AV-1451 正电子发射断层扫描保留与年龄和横截面 florbetapir 正电子发射断层扫描保留相关，但与受教育年限、性别或 APOE 基因型无关；（ii）在 parieto-temporal 和 precuneus 脑区 florbetapir 保留的年化变化增加，与 18F-AV-1451 正电子发射断层扫描扫描前的变化最显著相关，在整个队列中与颞下回和顶下小叶的 18F-AV-1451 PET 保留变化最大，florbetapir 阳性/阴性相关性；（iii）这种 18F-AV-1451 正电子发射断层扫描保留模式独立于 florbetapir 正电子发射断层扫描保留的相关年化变化，显著解释了认知表现和临床结果测量的变异性。这些发现与病理学文献一致，该文献表明 tau 缠结而不是淀粉样β斑块与认知和临床症状相关。此外，与淀粉样蛋白-β积累率增加相关的非局部关联与 tau 沉积增加相关，这非常有趣，并支持淀粉样蛋白-β病理学可能通过大脑的固有连通性网络对疾病病理学传播产生远程影响的观点。
