While blood-based tests are readily available for various conditions, including cardiovascular diseases, type 2 diabetes, and common cancers, Alzheimer’s disease (AD) and other neurodegenerative diseases lack an early blood-based screening test that can be used in primary care. Major efforts have been made towards the investigation of approaches that may lead to minimally invasive, cost-effective, and reliable tests capable of measuring brain pathological status. Here, we review past and current technologies developed to investigate biomarkers of AD, including novel blood-based approaches and the more established cerebrospinal fluid and neuroimaging biomarkers of disease. The utility of blood as a source of AD-related biomarkers in both clinical practice and interventional trials is discussed, supported by a comprehensive list of clinical trials for AD drugs and interventions that list biomarkers as primary or secondary endpoints. We highlight that identifying individuals in early preclinical AD using blood-based biomarkers will improve clinical trials and the optimization of therapeutic treatments as they become available. Lastly, we discuss challenges that remain in the field and address new approaches being developed, such as the examination of cargo packaged within extracellular vesicles of neuronal origin isolated from peripheral blood.

虽然基于血液的检测很容易用于各种疾病，包括心血管疾病、2 型糖尿病和常见癌症，但阿尔茨海默病 （AD） 和其他神经退行性疾病缺乏可用于初级保健的早期基于血液的筛查检测。已经做出了重大努力来研究可能导致能够测量脑病理状态的微创、经济高效且可靠的测试的方法。在这里，我们回顾了过去和当前为研究 AD 生物标志物而开发的技术，包括新的基于血液的方法和更成熟的脑脊液和神经影像学疾病生物标志物。讨论了血液在临床实践和干预试验中作为 AD 相关生物标志物来源的效用，并得到了将生物标志物列为主要或次要终点的 AD 药物和干预措施的综合临床试验列表的支持。我们强调，使用基于血液的生物标志物识别早期临床前 AD 中的个体将改进临床试验和治疗治疗的优化。最后，我们讨论了该领域仍然存在的挑战，并讨论了正在开发的新方法，例如检查从外周血中分离的神经元来源的细胞外囊泡内包装的货物。