Plasma Biomarkers for Alzheimer’s Disease Across the Continuum: A Systematic Review of SIMOA-Based Studies

Alzheimer's disease (AD) is the most common cause of dementia, and its overall incidence is rising as the proportion of older individuals in the population increases. Traditional diagnostic methods, such as lumbar puncture and neuroimaging, are costly and invasive, driving the search for blood-based biomarkers (BBB) for early diagnosis. The quantification of these biomarkers requires ultrasensitive techniques, such as the single-molecule array (SIMOA) platform. This systematic review synthesizes the available evidence on the biomarkers β-amyloid (Aβ42, Aβ40, and their ratio), tau protein (t-Tau, p-Tau181, p-Tau231, p-Tau217), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) in studies analyzing their blood concentrations using SIMOA, regardless of the platform model (SR-X, HD-1, HD-X). Findings support the potential of plasma biomarkers as an alternative or complement to invasive methods, although further validation is required before clinical implementation.