The blood biomarker breakthrough in Alzheimer's disease: what applications in 2026? Part I: Blood biomarkers transitioning to clinical practice

Alzheimer's disease (AD) is the leading cause of cognitive decline, and its diagnosis increasingly relies on a clinicobiological approach combining cognitive assessment with disease-specific biomarkers. Until recently, these biomarkers were mainly measured in cerebrospinal fluid (CSF), requiring lumbar puncture. Advances in ultrasensitive analytical technologies now enable their detection in blood, providing a less invasive, more accessible, and potentially earlier diagnostic alternative. This review summarizes the current state of blood-based biomarkers available for clinical use, focusing on markers of the amyloid pathway (Aβ1-42, Aβ1-40, and their ratio) and the Tau pathway (pTau181, pTau217, pTau231, and BD-Tau). Amyloid peptides reflect early amyloid pathology but show limited diagnostic performance when used alone. In contrast, phosphorylated Tau biomarkers, particularly pTau217 and the pTau217/Aβ1-42 ratio, demonstrate excellent diagnostic accuracy and strong correlations with established CSF and amyloid PET biomarkers. These blood biomarkers have recently been incorporated into national and international diagnostic recommendations and are progressively entering routine clinical practice. Their implementation represents a major advance in the diagnosis, patient stratification, and therapeutic monitoring of AD. Despite these promising developments, challenges remain regarding analytical standardization, interpretation thresholds, and ethical considerations related to very early diagnosis. Nevertheless, blood-based biomarkers are expected to play a central role in future Alzheimer's disease management and precision medicine strategies.