Region-Specific Hierarchy between Atrophy, Hypometabolism, and β-Amyloid (Aβ) Load in Alzheimer's Disease Dementia
Region-Specific Hierarchy between Atrophy, Hypometabolism, and β-Amyloid (Aβ) Load in Alzheimer's Disease Dementia
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DOI：
10.1523/jneurosci.2170-12.2012
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发表时间：
2012-11-14
影响因子：
5.3
通讯作者：
Chetelat, Gael
中科院分区：
文献类型：
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作者：
La Joie, Renaud;Perrotin, Audrey;Chetelat, Gael
灰质萎缩、葡萄糖代谢低下和β-淀粉样蛋白Aβ沉积是阿尔茨海默病的明显特征，但人们对它们之间的关系知之甚少。本研究旨在比较患有阿尔茨海默病的人类中这三种改变的局部水平。对来自 34 名淀粉样蛋白阴性健康对照者和 20 名很可能患有阿尔茨海默病病因的痴呆患者（使用最近推荐的神经影像生物标记物进行证明）的结构磁共振成像、F-18-氟脱氧葡萄糖正电子发射断层扫描 (PET) 和 F-18-氟倍他吡 PET 数据进行了分析。对于每位患者和成像方式，计算年龄调整的 Z 分数图，并进行直接的方式间体素比较和相关分析。大多数大脑区域的萎缩、代谢低下和 Aβ 沉积水平存在显着差异，但不同区域的层次结构有所不同。聚类分析揭示了不同的区域子集：（1）在海马体中，萎缩超过了代谢减退，而 Aβ 负荷最小； (2)在后联合区，Aβ沉积占主导地位，同时伴有高代谢低下和较低但仍然显着的萎缩； (3)在额叶区域，Aβ沉积最大，而结构和代谢变化较低。海马和颞顶叶皮层的萎缩和代谢低下显着相关，而 Aβ 负荷与萎缩或代谢低下均不显着相关。这些发现为 A β 负荷、代谢低下和萎缩之间的层次结构和关系的区域差异提供了直接证据。总而言之，这些差异可能反映了区域特异性病理或保护机制的差异参与，例如神经原纤维缠结、断开以及补偿过程的存在。
Gray matter atrophy, glucose hypometabolism, and beta-amyloid A beta deposition are well-described hallmarks of Alzheimer's disease, but their relationships are poorly understood. The present study aims to compare the local levels of these three alterations in humans with Alzheimer's disease. Structural magnetic resonance imaging, F-18-fluorodeoxyglucose positron emission tomography (PET), and F-18-florbetapir PET data from 34 amyloid-negative healthy controls and 20 demented patients with a high probability of Alzheimer's disease etiology (attested using neuroimaging biomarkers as recently recommended) were analyzed. For each patient and imaging modality, age-adjusted Z-score maps were computed, and direct between-modality voxelwise comparison and correlation analyses were performed. Significant differences in the levels of atrophy, hypometabolism, and A beta deposition were found in most brain areas, but the hierarchy differed across regions. A cluster analysis revealed distinct subsets of regions: (1) in the hippocampus, atrophy exceeded hypometabolism, whereas A beta load was minimal; (2) in posterior association areas, A beta deposition was predominant, together with high hypometabolism and lower but still significant atrophy; and (3) in frontal regions, A beta deposition was maximal, whereas structural and metabolic alterations were low. Atrophy and hypometabolism significantly correlated in the hippocampus and temporo-parietal cortex, whereas A beta load was not significantly related to either atrophy or hypometabolism. These findings provide direct evidence for regional variations in the hierarchy and relationships between A beta load, hypometabolism, and atrophy. Altogether, these variations probably reflect the differential involvement of region-specific pathological or protective mechanisms, such as the presence of neurofibrillary tangles, disconnection, as well as compensation processes.