In vivo staging of regional amyloid deposition.
In vivo staging of regional amyloid deposition.
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DOI：
10.1212/wnl.0000000000004643
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发表时间：
2017-11-14
期刊：
影响因子：
9.9
通讯作者：
Alzheimer's Disease Neuroimaging Initiative
中科院分区：
文献类型：
--
作者：
Grothe MJ;Barthel H;Sepulcre J;Dyrba M;Sabri O;Teipel SJ;Alzheimer's Disease Neuroimaging Initiative
根据淀粉样蛋白敏感的 PET 横截面数据估计淀粉样蛋白沉积的区域进展模式，并评估其对个体淀粉样蛋白病理学体内分期的潜力。对弗洛贝丕 (18F-AV45)-PET 数据进行多区域分析，用于确定来自阿尔茨海默病神经影像倡议队列的 667 名参与者样本中的个体淀粉样蛋白分布概况，其中包括认知正常的老年人 (CN) 以及患有轻度认知障碍和阿尔茨海默病 (AD) 痴呆的患者。 CN个体中区域淀粉样蛋白阳性的频率被用来构建进展淀粉样蛋白病理学的4阶段模型，并且个体分布概况被用来评估该分层阶段模型在整个队列中的一致性。根据四阶段模型，淀粉样蛋白沉积开始于颞基底和额内侧区域，并依次影响剩余的联合新皮质、初级感觉运动区域和内侧颞叶，最后影响纹状体。这些大脑区域中的淀粉样蛋白沉积显示出参与者之间高度一致的分层嵌套，其中只有 2% 的分布图谱偏离了分期方案。基于整体氟倍他吡-PET信号的传统二分分类方法大多错过了最早的体内淀粉样蛋白阶段，但与CSF Aβ42水平显着降低相关。体内晚期淀粉样蛋白阶段在 AD 患者中最常见，并且与非痴呆个体的认知障碍相关。参与者之间 PET 证明的淀粉样蛋白沉积高度一致的区域层次类似于神经病理学观察，并表明可预测的区域序列可用于分阶段个体体内淀粉样蛋白病理学的进展。
To estimate a regional progression pattern of amyloid deposition from cross-sectional amyloid-sensitive PET data and evaluate its potential for in vivo staging of an individual's amyloid pathology. Multiregional analysis of florbetapir (18F-AV45)–PET data was used to determine individual amyloid distribution profiles in a sample of 667 participants from the Alzheimer's Disease Neuroimaging Initiative cohort, including cognitively normal older individuals (CN) as well as patients with mild cognitive impairment and Alzheimer disease (AD) dementia. The frequency of regional amyloid positivity across CN individuals was used to construct a 4-stage model of progressing amyloid pathology, and individual distribution profiles were used to evaluate the consistency of this hierarchical stage model across the full cohort. According to a 4-stage model, amyloid deposition begins in temporobasal and frontomedial areas, and successively affects the remaining associative neocortex, primary sensory-motor areas and the medial temporal lobe, and finally the striatum. Amyloid deposition in these brain regions showed a highly consistent hierarchical nesting across participants, where only 2% exhibited distribution profiles that deviated from the staging scheme. The earliest in vivo amyloid stages were mostly missed by conventional dichotomous classification approaches based on global florbetapir-PET signal, but were associated with significantly reduced CSF Aβ42 levels. Advanced in vivo amyloid stages were most frequent in patients with AD and correlated with cognitive impairment in individuals without dementia. The highly consistent regional hierarchy of PET-evidenced amyloid deposition across participants resembles neuropathologic observations and suggests a predictable regional sequence that may be used to stage an individual's progress of amyloid pathology in vivo.