During the progression of Alzheimer’s disease (AD), neuropathology may propagate transneuronally, cause disruption in memory circuit, and lead to memory impairment. However, there is a lack of in vivo evidence regarding this process. Thus, we aim to simulate and observe the progression of neuropathology in AD continuum. We included cognitively normal (CN), mild cognitive impairments (MCI), and AD subjects, and further classified them using the A/T/N scheme (Group 0: CN, A − T−; Group 1: CN, A + T−; Group 2: CN, A + T+; Group 3: MCI, A + T+; Group 4: AD, A + T+). We investigated alterations of three core memory circuit structures: hippocampus (HP) subfields volume, cingulum-angular bundles (CAB) fiber integrity, and precuneus cortex volume. HP subfields volume showed the trend of initially increased and then decreased (starting from Group 2), while precuneus volume decreased in Groups 3 and 4. The CAB integrity degenerated in Groups 3 and 4 and aggravated with higher disease stages. Further, memory circuit impairments were correlated with neuropathology biomarkers and memory performance. Conclusively, our results demonstrated a pattern of memory circuit impairments along with AD progression: starting from the HP, then propagating to the downstream projection fiber tract and cortex. These findings support the tau propagation theory to some extent.

中文翻译：

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渐进性记忆回路损伤与阿尔茨海默病神经病理学传播：来自体内神经影像学的证据。

在阿尔茨海默病 (AD) 的进展过程中，神经病理学可能会跨神经元传播，导致记忆回路中断，并导致记忆障碍。然而，缺乏关于这一过程的体内证据。因此，我们的目标是模拟和观察 AD 连续体中神经病理学的进展。我们包括认知正常 (CN)、轻度认知障碍 (MCI) 和 AD 受试者，并使用 A/T/N 方案进一步对他们进行分类（第 0 组：CN，A - T-；第 1 组：CN，A + T -；第2组：CN，A+T+；第3组：MCI，A+T+；第4组：AD，A+T+）。我们研究了三个核心记忆电路结构的改变：海马 (HP) 子域体积、扣带角束 (CAB) 纤维完整性和楔前叶皮质体积。HP 子域体积呈现先增加后减少的趋势（从第 2 组开始），而第 3 和第 4 组的楔前叶体积减少。第 3 和第 4 组的 CAB 完整性退化，并随着疾病阶段的增加而加重。此外，记忆回路损伤与神经病理学生物标志物和记忆表现相关。最后，我们的结果证明了随着 AD 进展的记忆回路损伤模式：从 HP 开始，然后传播到下游的投射纤维束和皮层。这些发现在一定程度上支持了 tau 传播理论。我们的结果证明了随着 AD 进展的记忆回路损伤模式：从 HP 开始，然后传播到下游的投射纤维束和皮层。这些发现在一定程度上支持了 tau 传播理论。我们的结果证明了随着 AD 进展的记忆回路损伤模式：从 HP 开始，然后传播到下游的投射纤维束和皮层。这些发现在一定程度上支持了 tau 传播理论。