Blood-based biomarkers for Alzheimer's disease: Advances in early detection and monitoring of age-related neurodegeneration

IF 15.5 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews Pub Date : 2026-05-01 Epub Date: 2026-02-08 DOI:10.1016/j.arr.2026.103058

Wenting Fu , Paul Chi-Lui Ho

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引用次数: 0

Abstract

Alzheimer's disease (AD) presents a critical global challenge, accounting for over 60 % of the 57 million current dementia cases worldwide, with prevalence projected to exceed 100 million by 2050. Traditional diagnostic approaches, such as cerebrospinal fluid (CSF) analysis and neuroimaging are constrained by invasiveness, high costs, and limited accessibility, particularly problematic in aging population where early detection is crucial for effective intervention. This review synthesizes recent advances in blood-based biomarkers for AD, specifically phosphorylated tau proteins (p-tau217, p-tau181), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and the amyloid-β42/40 ratio. These minimally invasive biomarkers demonstrate exceptional diagnostic accuracy with p-tau217 achieving AUC values greater 0.93 and 91 % positive predictive value in detecting AD pathology, Critically, these biomarkers can identify pathological changes 15–20 years before symptom onset, with plasma p-tau217 levels increasing over 8.5 % annually during preclinical stages. We propose that dried blood spots (DBS), containing both arterial and venous blood components, offer superior representation of brain-derived substances at their first systematic distribution after cardiac output. Ultrasensitive technologies like Simoa and mass spectrometry now enable femtomolar-level detection, revolutionizing of AD diagnostics. However, challenges persist in assay standardization persist in assay standardization, and population-specific validation. Overcoming these barriers to integrate blood biomarkers with DBS technology represents a transformative shift toward accessible, scalable screening in aging communities, offering a paradigm shift in preventing age-related neurodegeneration through early detection and timely intervention.

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阿尔茨海默病的血液生物标志物：与年龄相关的神经变性的早期检测和监测进展

阿尔茨海默病（AD）是一项重大的全球挑战，占目前全球5700万痴呆病例的60% 以上，预计到2050年患病率将超过1亿。传统的诊断方法，如脑脊液（CSF）分析和神经成像，受到侵入性、高成本和有限可及性的限制，特别是在早期发现对有效干预至关重要的老龄化人口中存在问题。本文综述了AD血液生物标志物的最新进展，特别是磷酸化tau蛋白（p-tau217, p-tau181），神经丝轻链（NfL），胶质纤维酸性蛋白（GFAP）和淀粉样蛋白-β42/40比率。这些微创生物标志物显示出卓越的诊断准确性，p-tau217在检测AD病理方面的AUC值大于0.93和91% %的阳性预测值。关键的是，这些生物标志物可以在症状出现前15-20年识别病理变化，血浆p-tau217水平在临床前阶段每年增加8.5 %以上。我们提出，含有动脉和静脉血成分的干血斑（DBS）在心输出量后的第一次系统分布中提供了脑源性物质的优越代表。像Simoa和质谱这样的超灵敏技术现在可以实现飞摩尔级别的检测，彻底改变AD的诊断。然而，在分析标准化和人群特异性验证方面，挑战仍然存在。克服这些障碍，将血液生物标志物与DBS技术结合起来，代表着在老龄化社区向可获得、可扩展的筛查转变，为通过早期检测和及时干预预防与年龄相关的神经退行性疾病提供了一种范式转变。

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

Ageing Research Reviews 医学-老年医学

CiteScore

19.80

自引率

2.30%

发文量

216

审稿时长

55 days

期刊介绍： With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends. ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research. The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.