Afrin Meher Rijwana, Upadhyaya Pankaj Ghritakousik, Hashim Abdul, Bhattacharya Kunal, Chanu Nongmaithem Randhoni, Das Dibyajyoti, Khanal Pukar, Deka Satyendra
Pratiksha Institute of Pharmaceutical Sciences, Guwahati, Assam 781026, India.
Pratiksha Institute of Pharmaceutical Sciences, Guwahati, Assam 781026, India; Royal School of Pharmacy, The Assam Royal Global University, Guwahati, Assam 781035, India.
Ageing Res Rev. 2025 Jun;108:102736. doi: 10.1016/j.arr.2025.102736. Epub 2025 Mar 22.
Alzheimer's disease (AD) is the most common neurodegenerative disorder that leads to progressive cognitive decline and imposes a significant socio-economic burden. Traditional diagnostic methods, primarily based on amyloid-beta (Aβ) and tau biomarkers, often identify the disease at late stages, highlighting the need for more sensitive and accessible early detection tools. This review explores emerging non-traditional biomarkers, including salivary, lipid, urinary, synaptic, blood-based, microRNA (miRNA), cerebrospinal fluid (CSF), fecal, and inflammatory markers, which provide deeper insights into AD pathophysiology. These biomarkers reflect key pathological processes such as neuroinflammation, mitochondrial dysfunction, oxidative stress, synaptic damage, lipid dysregulation, and genetic factors. Non-invasive biomarkers, such as those found in saliva and urine, present promising avenues for large-scale screening, while advanced blood-based markers like neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) offer precise monitoring of neurodegeneration and inflammation. Additionally, miRNAs and lipid biomarkers shed light on molecular alterations in neuronal health and signaling. Integrating these biomarkers with imaging techniques, proteomics, and genetic profiling enhances diagnostic accuracy and enables personalized treatment approaches. This shift toward multi-dimensional biomarker assessment not only improves early detection but also aids in tailoring therapeutic strategies to individual disease profiles. By reviewing recent advancements, this article highlights the transformative potential of emerging biomarkers in overcoming the limitations of conventional diagnostics. Standardization and validation across diverse populations will be crucial in expanding their clinical applicability, ultimately improving disease management, reducing societal burden, and enhancing the quality of life for individuals affected by AD.
阿尔茨海默病（AD）是最常见的神经退行性疾病，会导致进行性认知衰退，并带来重大的社会经济负担。传统的诊断方法主要基于β-淀粉样蛋白（Aβ）和tau生物标志物，往往在疾病晚期才能确诊，这凸显了对更敏感、更易获取的早期检测工具的需求。本综述探讨了新兴的非传统生物标志物，包括唾液、脂质、尿液、突触、血液、微小RNA（miRNA）、脑脊液（CSF）、粪便和炎症标志物，这些标志物能更深入地了解AD的病理生理学。这些生物标志物反映了神经炎症、线粒体功能障碍、氧化应激、突触损伤、脂质失调和遗传因素等关键病理过程。唾液和尿液中的非侵入性生物标志物为大规模筛查提供了有前景的途径，而神经丝轻链（NfL）和胶质纤维酸性蛋白（GFAP）等先进的血液标志物则能精确监测神经退行性变和炎症。此外，miRNA和脂质生物标志物揭示了神经元健康和信号传导中的分子变化。将这些生物标志物与成像技术、蛋白质组学和基因分析相结合，可提高诊断准确性，并实现个性化治疗方法。这种向多维生物标志物评估的转变不仅能改善早期检测，还有助于根据个体疾病特征制定治疗策略。通过回顾近期进展，本文强调了新兴生物标志物在克服传统诊断局限性方面的变革潜力。在不同人群中进行标准化和验证对于扩大其临床应用至关重要，最终可改善疾病管理、减轻社会负担并提高AD患者的生活质量。
