The Role of Blood-Based Biomarkers in Transforming Alzheimer's Disease Research and Clinical Management: A Review.

Alzheimer's disease (AD) is a progressive neurodegenerative condition representing the most common cause of dementia and currently affects millions of people worldwide. The clinical presentation includes memory impairment, cognitive decline, and neuropsychiatric symptoms, reflecting pathological hallmarks such as β-amyloid (Aβ) plaques, neurofibrillary tangles, synaptic dysfunction, and neuroinflammation. Despite being the gold standard for detecting amyloid and tau pathologies in vivo, cerebrospinal fluid (CSF) biomarkers and positron emission tomography (PET) imaging are not widely used in the clinical setting because of invasiveness, high costs, and restricted accessibility. Recent advances in blood-based biomarkers offer a promising and minimally invasive tool for early detection, diagnosis, and monitoring of AD. Ultra-sensitive analytical platforms, including single-molecule arrays (Simoa) and immunoprecipitation-mass spectrometry, now enable reliable quantification of plasma Aβ isoforms, phosphorylated tau variants (p-Tau181, p-Tau217, p-Tau231), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP). In addition, blood biomarkers reflecting oxidative stress, neuroinflammation, synaptic disruption and metabolic dysfunction are under active investigation. This narrative review synthesizes current evidence on blood-based biomarkers in AD, emphasizing their biological relevance, diagnostic accuracy, and clinical applications. Finally, we highlight forthcoming challenges, such as standardization, and future directions, including the use of artificial intelligence in precision medicine.