Thalamic pathology and memory loss in early Alzheimer's disease: moving the focus from the medial temporal lobe to Papez circuit.
Thalamic pathology and memory loss in early Alzheimer's disease: moving the focus from the medial temporal lobe to Papez circuit.
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DOI：
10.1093/brain/aww083
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发表时间：
2016-07
期刊：
影响因子：
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通讯作者：
Hornberger M
中科院分区：
文献类型：
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作者：
Aggleton JP;Pralus A;Nelson AJ;Hornberger M
对阿尔茨海默病情景性记忆丧失的研究一再集中在海马体上。Aggleton等人认为，这种方法过于狭隘，忽略了其他大脑部位的早期参与，最明显的是丘脑前核，这对情景记忆也至关重要。对阿尔茨海默病情景性记忆丧失的研究一再集中在海马体上。Aggleton等人认为，这种方法过于狭隘，忽略了其他大脑部位的早期参与，最明显的是丘脑前核，这对情景记忆也至关重要。人们普遍认为，内侧颞叶的早期蛋白质病理引发了阿尔茨海默病情景记忆的丧失，这是这类痴呆症中最早的认知缺陷之一。在这个区域内，海马体被认为是情景记忆最重要的区域。因此，对阿尔茨海默病中记忆丧失的原因的研究继续集中在海马功能障碍以及该区域的疾病修饰疗法如何潜在地减轻记忆症状。本综述通过汇集尸检研究、非侵入性成像（包括症状前、高危病例的研究）和转基因动物模型的研究结果，对这一根深蒂固的观念提出了质疑。综合证据表明，早期阿尔茨海默病情景记忆的丧失反映了扩展记忆系统（Papez回路）更广泛的神经退行性变，该系统主要涉及边缘丘脑。在这个系统中，丘脑前核是突出的，因为它们对情景记忆的重要贡献，以及这些核在前驱阿尔茨海默病中如何显得脆弱。由于丘脑异常发生在疾病的一些早期阶段，这种变化仅仅是继发于内侧颞叶功能障碍的想法受到了挑战。考虑到后皮层区域的功能障碍如何提供一些最早的前驱阿尔茨海默病的体内成像证据，丘脑前核和脾后皮层之间的相互依赖关系进一步加强了这种替代观点。认识到丘脑前核对记忆和注意力的重要性，可以让我们对阿尔茨海默病有更平衡的了解。此外，重新关注边缘丘脑，以及帕佩兹回路的其余部分，将对阿尔茨海默病认知症状的诊断、建模和实验治疗产生重大影响。
Research into episodic memory loss in Alzheimer’s disease has repeatedly focused on the hippocampus. Aggleton et al. argue that this approach is too narrow, and ignores the early involvement of other brain sites, most notably the anterior thalamic nuclei, which are also vital for episodic memory. Research into episodic memory loss in Alzheimer’s disease has repeatedly focused on the hippocampus. Aggleton et al. argue that this approach is too narrow, and ignores the early involvement of other brain sites, most notably the anterior thalamic nuclei, which are also vital for episodic memory. It is widely assumed that incipient protein pathology in the medial temporal lobe instigates the loss of episodic memory in Alzheimer’s disease, one of the earliest cognitive deficits in this type of dementia. Within this region, the hippocampus is seen as the most vital for episodic memory. Consequently, research into the causes of memory loss in Alzheimer’s disease continues to centre on hippocampal dysfunction and how disease-modifying therapies in this region can potentially alleviate memory symptomology. The present review questions this entrenched notion by bringing together findings from post-mortem studies, non-invasive imaging (including studies of presymptomatic, at-risk cases) and genetically modified animal models. The combined evidence indicates that the loss of episodic memory in early Alzheimer’s disease reflects much wider neurodegeneration in an extended mnemonic system (Papez circuit), which critically involves the limbic thalamus. Within this system, the anterior thalamic nuclei are prominent, both for their vital contributions to episodic memory and for how these same nuclei appear vulnerable in prodromal Alzheimer’s disease. As thalamic abnormalities occur in some of the earliest stages of the disease, the idea that such changes are merely secondary to medial temporal lobe dysfunctions is challenged. This alternate view is further strengthened by the interdependent relationship between the anterior thalamic nuclei and retrosplenial cortex, given how dysfunctions in the latter cortical area provide some of the earliest in vivo imaging evidence of prodromal Alzheimer’s disease. Appreciating the importance of the anterior thalamic nuclei for memory and attention provides a more balanced understanding of Alzheimer’s disease. Furthermore, this refocus on the limbic thalamus, as well as the rest of Papez circuit, would have significant implications for the diagnostics, modelling, and experimental treatment of cognitive symptoms in Alzheimer’s disease.