Ma Ya-Nan, Xia Ying, Karako Kenji, Song Peipei, Tang Wei, Hu Xiqi
Department of Neurosurgery, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou, China.
Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Biosci Trends. 2025 Mar 6;19(1):1-9. doi: 10.5582/bst.2024.01365. Epub 2025 Jan 23.
Alzheimer's disease (AD), the leading cause of dementia, significantly impacts global public health, with cases expected to exceed 150 million by 2050. Late-onset Alzheimer's disease (LOAD), predominantly influenced by the APOE-ε4 allele, exhibits complex pathogenesis involving amyloid-β (Aβ) plaques, neurofibrillary tangles (NFTs), neuroinflammation, and blood-brain barrier (BBB) disruption. Proteomics has emerged as a pivotal technology in uncovering molecular mechanisms and identifying biomarkers for early diagnosis and intervention in AD. This paper reviews the genetic and molecular roles of APOE-ε4 in the pathology of AD, including its effects on Aβ aggregation, tau phosphorylation, neuroinflammation, and BBB integrity. Additionally, it highlights recent advances in serum proteomics, revealing APOE-ε4-dependent and independent protein signatures with potential as early biomarkers for AD. Despite technological progress, challenges such as population diversity, standardization, and distinguishing AD-specific biomarkers remain. Directions for future research emphasize multicenter longitudinal studies, multi-omics integration, and the clinical translation of proteomic findings to enable early detection of AD and personalized treatment strategies. Proteomics advances in AD research hold the promise of improving patient outcomes and reducing the global disease burden.
阿尔茨海默病（AD）是痴呆症的主要病因，对全球公共卫生产生重大影响，预计到2050年病例数将超过1.5亿。晚发性阿尔茨海默病（LOAD）主要受APOE-ε4等位基因影响，其发病机制复杂，涉及淀粉样β蛋白（Aβ）斑块、神经原纤维缠结（NFTs）、神经炎症和血脑屏障（BBB）破坏。蛋白质组学已成为揭示AD分子机制以及识别早期诊断和干预生物标志物的关键技术。本文综述了APOE-ε4在AD病理中的遗传和分子作用，包括其对Aβ聚集、tau蛋白磷酸化、神经炎症和BBB完整性的影响。此外，还强调了血清蛋白质组学的最新进展，揭示了具有作为AD早期生物标志物潜力的APOE-ε4依赖性和独立性蛋白质特征。尽管技术取得了进步，但仍存在诸如人群多样性、标准化以及区分AD特异性生物标志物等挑战。未来研究方向强调多中心纵向研究、多组学整合以及蛋白质组学研究结果的临床转化，以实现AD的早期检测和个性化治疗策略。AD研究中的蛋白质组学进展有望改善患者预后并减轻全球疾病负担。
