Hulshof Lianne A, van Nuijs Danny, Hol Elly M, Middeldorp Jinte
Department of Translational Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, Netherlands.
Department Neurobiology and Aging, Biomedical Primate Research Centre, Rijswijk, Netherlands.
Front Cell Neurosci. 2022 Jun 16;16:899251. doi: 10.3389/fncel.2022.899251. eCollection 2022.
Alzheimer's disease (AD) is the most common cause of dementia, affecting 35 million people worldwide. One pathological feature of progressing AD is the loss of synapses. This is the strongest correlate of cognitive decline. Astrocytes, as an essential part of the tripartite synapse, play a role in synapse formation, maintenance, and elimination. During AD, astrocytes get a reactive phenotype with an altered gene expression profile and changed function compared to healthy astrocytes. This process likely affects their interaction with synapses. This systematic review aims to provide an overview of the scientific literature including information on how astrocytes affect synapse formation and elimination in the brain of AD patients and in animal models of the disease. We review molecular and cellular changes in AD astrocytes and conclude that these predominantly result in lower synapse numbers, indicative of decreased synapse support or even synaptotoxicity, or increased elimination, resulting in synapse loss, and consequential cognitive decline, as associated with AD. Preventing AD induced changes in astrocytes might therefore be a potential therapeutic target for dementia. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=148278, identifier [CRD148278].
阿尔茨海默病（AD）是痴呆最常见的病因，全球有3500万人受其影响。进展性AD的一个病理特征是突触丧失。这是认知衰退最密切的相关因素。星形胶质细胞作为三联突触的重要组成部分，在突触形成、维持和消除中发挥作用。在AD期间，星形胶质细胞呈现反应性表型，与健康星形胶质细胞相比，其基因表达谱改变且功能发生变化。这一过程可能会影响它们与突触的相互作用。本系统评价旨在概述科学文献，包括有关星形胶质细胞如何影响AD患者大脑和该疾病动物模型中突触形成和消除的信息。我们回顾了AD星形胶质细胞的分子和细胞变化，并得出结论，这些变化主要导致突触数量减少，表明突触支持减少甚至存在突触毒性，或导致消除增加，从而导致突触丧失以及随之而来的认知衰退，这与AD相关。因此，预防AD诱导的星形胶质细胞变化可能是痴呆的一个潜在治疗靶点。https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=148278，标识符[CRD148278]
