Plasma-based diagnostic and screening platform using a combination of biosensing signals in Alzheimer's disease

Abstract

Using biosensor to screen for Alzheimer's disease (AD) facilitates early detection of AD with high sensitivity and accuracy. This approach overcomes the limitations of conventional AD diagnostic methods, such as neuropsychological assessment and neuroimaging analysis. Here, we propose a simultaneous analysis of signal combinations generated by four crucial AD biomarkers (Amyloid beta 1-40 (Aβ₄₀), Aβ₄₂, total tau 441 (tTau₄₄₁), and phosphorylated tau 181 (pTau₁₈₁)) by inducing a dielectrophoretic (DEP) force on fabricated interdigitated microelectrode (IME) sensor. By applying an optimal DEP force, our biosensor selectively concentrates and filters the plasma-based AD biomarkers, exhibiting high sensitivity (limit of detection <100 fM) and selectivity in the plasma-based AD biomarkers detection (p < 0.0001). Consequently, it is demonstrated that a complex combined signal comprising four AD-specific biomarker signals (Aβ₄₀- Aβ₄₂+ tTau₄₄₁- pTau₁₈₁) can differentiate between patients with AD and healthy subjects with high accuracy (78.85%) and precision (80.95%) (p < 0.0001).

Keywords: Alzheimer's disease; Amyloid beta; Dielectrophoresis; Interdigitated microelectrode; Multiplexed detection; Tau.