Ultrasensitive and point-of-care detection of plasma phosphorylated tau in Alzheimer's disease using colorimetric and surface-enhanced Raman scattering dual-readout lateral flow assay

Phosphorylation of tau at Ser (396, 404) (p-tau(396,404)) is one of the earliest phosphorylation events, and plasma p-tau(396,404) level appears to be a potentially promising biomarker of Alzheimer's disease (AD). The low abundance and easy degradation of p-tau in the plasma make the lateral flow assay (LFA) a suitable choice for point-of-care detection of plasma p-tau(396,404) levels. Herein, based on our screening of a pair of p-tau(396,404)-specific antibodies, we developed a colorimetric and surface-enhanced Raman scattering (SERS) dual-readout LFA for the rapid, highly sensitive, and robust detection of plasma p-tau(396,404) levels. This LFA realized a detection limit of 60 pg/mL by the naked eye or 3.8 pg/mL by SERS without cross-reacting with other tau species. More importantly, LFA rapidly and accurately differentiated AD patients from healthy controls, suggesting that it has the potential for clinical point-of-care application in AD diagnosis. This dual-readout LFA has the advantages of simple operation, rapid, and ultra-sensitive detection, providing a new way for early AD diagnosis and intervention, especially in primary and community AD screening.

Automated summary

Phosphorylation of tau at Ser(396,404) is an early event in Alzheimer's disease (AD), and plasma p-tau(396,404) level could be a potential biomarker for AD. Researchers developed a dual-output lateral flow assay (LFA) that combines colorimetric and surface-enhanced Raman scattering (SERS) for the rapid, sensitive, and robust detection of plasma p-tau(396,404) levels. The LFA showed a detection limit of 60 pg/mL by the naked eye or 3.8 pg/mL by SERS, with no cross-reactivity with other tau species. This LFA could differentiate AD patients from healthy controls, suggesting its potential for point-of-care AD diagnosis.