Da Conceicao Anna R R, Marinatto Júlia, Pinheiro Lisandra S, Rody Tayna, De Felice Fernanda G
Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
D'Or Institute for Research and Education, Rio de Janeiro, Brazil.
J Neurochem. 2025 Aug;169(8):e70209. doi: 10.1111/jnc.70209.
Extracellular vesicles (EVs) are lipid bilayer nano- to micro-sized particles that carry biomolecules, such as proteins, lipids, and genetic material. Their composition depends on the cellular microenvironment and the health status of tissues. EVs are released by different cell types under distinct circumstances, mediating intercellular communication in both physiological and pathological contexts. In Alzheimer's disease (AD), EVs have been shown to influence pathological events, carrying neurotoxins, such as neuroinflammatory factors, pathogenic forms of amyloid-β, and phosphorylated tau into recipient neurons. This contributes to the propagation of AD pathology and exacerbates neuronal degeneration. However, under physiological conditions, EVs play key roles in maintaining tissue homeostasis. In the central nervous system (CNS), EVs derived from glial cells and neurons modulate synaptic plasticity and neuronal activity. Interestingly, EVs carrying neurotoxin molecules can cross the blood-brain barrier, making them attractive candidates as biomarkers for diagnosis with a minimally invasive approach to assess CNS alterations. Additionally, EVs contribute to the activation of neuroprotective pathways, participating in the periphery-to-brain signaling. Notably, alteration of EV content has been further proposed to have potential therapeutic applications. Herein, we summarize the multifaceted role of EVs in AD, emphasizing their role in promoting neuroprotection and exploring their contribution to our understanding of AD pathophysiology.
细胞外囊泡（EVs）是脂质双层包裹的纳米到微米大小的颗粒，携带生物分子，如蛋白质、脂质和遗传物质。它们的组成取决于细胞微环境和组织的健康状况。EVs在不同情况下由不同细胞类型释放，在生理和病理环境中介导细胞间通讯。在阿尔茨海默病（AD）中，EVs已被证明会影响病理事件，将神经毒素，如神经炎症因子、淀粉样β蛋白的致病形式和磷酸化tau蛋白携带到受体神经元中。这有助于AD病理的传播并加剧神经元变性。然而，在生理条件下，EVs在维持组织稳态中起关键作用。在中枢神经系统（CNS）中，源自神经胶质细胞和神经元的EVs调节突触可塑性和神经元活动。有趣的是，携带神经毒素分子的EVs可以穿过血脑屏障，使其成为通过微创方法诊断以评估CNS改变的有吸引力的生物标志物候选物。此外，EVs有助于神经保护途径的激活，参与外周到脑的信号传导。值得注意的是，进一步提出EVs内容物的改变具有潜在的治疗应用。在此，我们总结了EVs在AD中的多方面作用，强调它们在促进神经保护中的作用，并探讨它们对我们理解AD病理生理学的贡献。
