School of Biomedical Engineering, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, South Korea.
Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, 20 Eonjuro 63-gil, Gangnam-gu, Seoul, South Korea.
Alzheimers Res Ther. 2022 Sep 2;14(1):121. doi: 10.1186/s13195-022-01061-0.
The clinical features of Alzheimer's disease (AD) vary substantially depending on whether the onset of cognitive deficits is early or late. The amount and distribution patterns of tau pathology are thought to play a key role in the clinical characteristics of AD, which spreads throughout the large-scale brain network. Here, we describe the differences between tau-spreading processes in early- and late-onset symptomatic individuals on the AD spectrum.
We divided 74 cognitively unimpaired (CU) and 68 cognitively impaired (CI) patients receiving F-flortaucipir positron emission tomography scans into two groups by age and age at onset. Members of each group were arranged in a pseudo-longitudinal order based on baseline tau pathology severity, and potential interregional tau-spreading pathways were defined following the order using longitudinal tau uptake. We detected a multilayer community structure through consecutive tau-spreading networks to identify spatio-temporal changes in the propagation hubs.
In each group, ordered tau-spreading networks revealed the stage-dependent dynamics of tau propagation, supporting distinct tau accumulation patterns. In the young CU/early-onset CI group, tau appears to spread through a combination of three independent communities with partially overlapped territories, whose specific driving regions were the basal temporal regions, left medial and lateral temporal regions, and left parietal regions. For the old CU/late-onset CI group, however, continuation of major communities occurs in line with the appearance of hub regions in the order of bilateral entorhinal cortices, parahippocampal and fusiform gyri, and lateral temporal regions.
Longitudinal tau propagation depicts distinct spreading pathways of the early- and late-onset AD spectrum characterized by the specific location and appearance period of several hub regions that dominantly provide tau.
阿尔茨海默病（AD）的临床特征因认知障碍的起始时间是早还是晚而有很大差异。tau 病理学的数量和分布模式被认为在 AD 的临床特征中起着关键作用，AD 会在整个大规模脑网络中扩散。在这里，我们描述了 AD 谱中早发性和晚发性有症状个体的 tau 扩散过程之间的差异。
我们将 74 名认知正常（CU）和 68 名认知受损（CI）接受 F-flortaucipir 正电子发射断层扫描的患者按年龄和发病年龄分为两组。根据基线 tau 病理学严重程度，每组中的成员按伪纵向顺序排列，并根据纵向 tau 摄取顺序定义潜在的区域间 tau 扩散途径。我们通过连续的 tau 扩散网络检测到多层社区结构，以识别传播枢纽的时空变化。
在每个组中，有序的 tau 扩散网络揭示了 tau 传播的阶段依赖性动态，支持不同的 tau 积累模式。在年轻的 CU/早发性 CI 组中，tau 似乎通过三个具有部分重叠区域的独立社区的组合传播，其特定的驱动区域是基底颞区、左侧内侧和外侧颞区以及左侧顶区。然而，对于老年 CU/晚发性 CI 组，主要社区的延续与双侧内嗅皮质、海马旁回和梭状回以及外侧颞区的枢纽区域的出现一致。
纵向 tau 传播描绘了早发性和晚发性 AD 谱的不同扩散途径，其特征是几个枢纽区域的特定位置和出现时间，这些区域主要提供 tau。
