Role of the gut microbiome in mediating sex-specific differences in the pathophysiology of Alzheimer's disease.

IF 5.6 2区医学 Q1 CLINICAL NEUROLOGY

Neurotherapeutics Pub Date : 2024-10-01 Epub Date: 2024-07-25 DOI:10.1016/j.neurot.2024.e00426

Piyali Saha, Sangram S Sisodia

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引用次数: 0

Abstract

Alzheimer's disease (AD) presents distinct pathophysiological features influenced by biological sex, with women disproportionately affected due to sex-specific genetic, hormonal, and epigenetic factors. This review delves into three critical areas of sex differences in AD: First, we explore how genetic predisposition and hormonal changes, particularly those involving sex-specific modifications, influence susceptibility and progression of the disease. Second, we examine the neuroimmune dynamics in AD, emphasizing variations in microglial activity between sexes during crucial developmental stages and the effects of hormonal interventions on disease outcomes. Crucially, this review highlights the significant role of gut microbiome perturbations in shaping AD pathophysiology in a sex-specific manner, suggesting that these alterations can further influence microglial activity and overall disease trajectory. Third, we provide a viewpoint that advocates for personalized therapeutic strategies that integrate the understanding of hormonal fluctuations and microbiome dynamics into treatment plans in order to optimize patient outcomes.

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肠道微生物组在阿尔茨海默病病理生理学中介导性别差异的作用。

阿尔茨海默病（AD）受生理性别的影响而呈现出不同的病理生理学特征，由于特定性别的遗传、荷尔蒙和表观遗传因素，女性受到的影响更大。本综述将深入探讨 AD 性别差异的三个关键领域：首先，我们探讨遗传易感性和激素变化，尤其是涉及性别特异性修饰的变化，如何影响疾病的易感性和进展。其次，我们研究了 AD 的神经免疫动态，强调了在关键发育阶段两性之间微胶质细胞活动的差异，以及激素干预对疾病结果的影响。最重要的是，这篇综述强调了肠道微生物组的扰动在以性别特异性的方式塑造 AD 病理生理学方面的重要作用，表明这些改变会进一步影响微胶质细胞的活性和整个疾病的发展轨迹。第三，我们提出了一种观点，主张采用个性化治疗策略，将对激素波动和微生物组动态的了解融入治疗计划中，以优化患者的预后。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neurotherapeutics 医学-神经科学

CiteScore

11.00

自引率

3.50%

发文量

154

审稿时长

6-12 weeks

期刊介绍： Neurotherapeutics® is the journal of the American Society for Experimental Neurotherapeutics (ASENT). Each issue provides critical reviews of an important topic relating to the treatment of neurological disorders written by international authorities. The Journal also publishes original research articles in translational neuroscience including descriptions of cutting edge therapies that cross disciplinary lines and represent important contributions to neurotherapeutics for medical practitioners and other researchers in the field. Neurotherapeutics ® delivers a multidisciplinary perspective on the frontiers of translational neuroscience, provides perspectives on current research and practice, and covers social and ethical as well as scientific issues.