Potential neural substrates underlying circadian and olfactory disruptions in preclinical Alzheimer's disease.
Potential neural substrates underlying circadian and olfactory disruptions in preclinical Alzheimer's disease.
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DOI：
10.3389/fnins.2023.1295998
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发表时间：
2023
影响因子：
4.3
通讯作者：
Todd, William D.
中科院分区：
文献类型：
--
作者：
Jeffs, Quiana L.;Prather, Jonathan F.;Todd, William D.
关键词：
阿尔茨海默病（AD）是痴呆症的主要原因，全球有超过4500万患者，并对患者和护理人员造成重大的经济和情感负担，显著增加了受影响的人数。不幸的是，许多现有的研究对这种疾病只解决了一小部分相关的神经病学和病理学。在这篇综述中，我们建议针对疾病的最早阶段，当神经病学首次出现。在这些阶段中，在AD的标志性症状如认知障碍和记忆丧失发作之前，昼夜节律和嗅觉中断出现并且是可检测的。昼夜节律和嗅觉系统之间的功能相似性提供了一个基础，在此基础上寻找AD中的共同机制，这些机制可能在疾病的早期就针对它们。现有的研究这些系统之间的相互作用，而有趣的，留下开放的问题，神经基板的基础。这种相互作用的潜在底物提出了在这篇评论中，如间接的预测，可能在功能上连接两个系统和多巴胺能信号。这些底物可能对AD早期昼夜节律和嗅觉功能中断的机制有重要意义。在这篇综述中，我们建议早期检测AD使用的昼夜节律和嗅觉缺陷和随后的早期治疗这些缺陷的组合可能会提供深刻的好处，患者和照顾者。此外，我们建议，针对AD中这两个系统的交叉点的研究可以揭示目前逃避研究人员的更广泛的症状和病理的机制。
Alzheimer’s disease (AD) is the leading cause of dementia, with over 45 million patients worldwide, and poses significant economic and emotional burdens to both patients and caregivers, significantly raising the number of those affected. Unfortunately, much of the existing research on the disease only addresses a small subset of associated symptomologies and pathologies. In this review, we propose to target the earliest stages of the disease, when symptomology first arises. In these stages, before the onset of hallmark symptoms of AD such as cognitive impairments and memory loss, circadian and olfactory disruptions arise and are detectable. Functional similarities between circadian and olfactory systems provide a basis upon which to seek out common mechanisms in AD which may target them early on in the disease. Existing studies of interactions between these systems, while intriguing, leave open the question of the neural substrates underlying them. Potential substrates for such interactions are proposed in this review, such as indirect projections that may functionally connect the two systems and dopaminergic signaling. These substrates may have significant implications for mechanisms underlying disruptions to circadian and olfactory function in early stages of AD. In this review, we propose early detection of AD using a combination of circadian and olfactory deficits and subsequent early treatment of these deficits may provide profound benefits to both patients and caregivers. Additionally, we suggest that targeting research toward the intersection of these two systems in AD could uncover mechanisms underlying the broader set of symptoms and pathologies that currently elude researchers.
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